Search

ObjectivesTo evaluate long-term kinetics of the BNT162b2 mRNA vaccine-induced immune response in adult patients with autoimmune inflammatory rheumatic diseases (AIIRD) and immunocompetent controls.MethodsA prospective multicentre study investigated serum anti-SARS-CoV-2 S1/S2 IgG titre at 2–6 weeks (AIIRD n=720, controls n=122) and 6 months (AIIRD n=628, controls n=116) after the second vaccine, and 2–6 weeks after the third vaccine dose (AIIRD n=169, controls n=45). T-cell immune response to the third vaccine was evaluated in a small sample.ResultsThe two-dose vaccine regimen induced a higher humoral response in controls compared with patients, postvaccination seropositivity rates of 100% versus 84.72%, pConclusionsThe two-dose BNTb262 regimen was associated with similar clinical efficacy and similar waning of the humoral response over 6 months among patients with AIIRD and controls. The third vaccine dose restored the humoral response in all of the controls and the majority of patients.

Patients with inflammatory rheumatic and musculoskeletal diseases (iRMDs) are often treated with immunomodulatory or immunosuppressive medications; consequently, they have been excluded alongside other immunocompromised patients from late stages of SARS-CoV-2 vaccine trials. SARS-CoV-2 vaccine efficacy in this population is unclear, though initial data are reassuring overall. However, a slightly lower SARS-CoV-2 immunogenicity of vaccines has been documented in some patients with iRMD.1 2 Some common rheumatic and musculoskeletal disease (RMD) medications have been highlighted as possible influential factors on immunogenicity, particularly rituximab (RTX), mycophenolate mofetil (MMF), methotrexate (MTX), abatacept and glucocorticoids.3–7 The European Alliance of Associations for Rheumatology (EULAR) launched a COVID-19 registry in March 2020, capturing COVID-19 outcomes in the European RMD population. Questions on reinfection and vaccination were added in January 2021. A further EULAR registry (COVAX) was launched in February 2021 to collect data on COVID-19 vaccination and related adverse events among patients with RMD. Here we describe a series of patients who contracted SARS-CoV-2 infection after COVID-19 vaccination between 19 January 2021 and 27 July 2021. The series consists of 38 adults with iRMDs, 8 from the COVID-19 registry (

BackgroundHepatitis B surface antigen (HBsAg) reverse seroconversion (RS) can happen in patients with rheumatoid arthritis (RA) with resolved hepatitis B (RHB) undergoing biological disease-modifying antirheumatic drugs (bDMARDs). But the incidence and risk factors need to be delineated.MethodsFrom 2003 to 2019, 1937 patients with RA with available HBsAg and antibody to hepatitis B virus (HBV) core antigen data were retrospectively reviewed, and 489 patients with RHB undergoing bDMARDs treatment were identified. Factors associated with HBsAg RS were analysed.ResultsDuring 67 828 person-months of follow-up, 27 (5.5%) patients developed HBsAg RS after bDMARD treatment. As compared with those without HBsAg RS, patients with HBsAg RS were older, had lower frequency of antibody to HBsAg (anti-HBs), and lower baseline anti-HBs levels. In multivariate analysis, rituximab, abatacept and baseline negative for anti-HBs were the independent risk factors for HBsAg RS (adjusted HR: 87.76, 95% CI: 11.50 to 669.73, pConclusionsNot only rituximab, but also abatacept has a high risk of HBV reactivation in patient with RA with RHB. Anti-HBs positivity cannot confer HBV reactivation-free status if the anti-HBs levels are not high enough for patients with RHB on rituximab and abatacept treatment.

Dear Editor, A potential association between rituximab and more severe COVID-19 outcomes has been previously raised, based on case reports, retrospective studies and mostly declarative registries.1–4 To further investigate this association, we focused on patients with inflammatory arthritides (IA) receiving intravenous biological agents at day hospitals to limit selection and recall bias, as well as missing data. All patients with IA treated in day hospitals with intravenous biological agents (rituximab, abatacept, infliximab or tocilizumab) in seven clinical centres in France (Strasbourg, Colmar, Mulhouse, Nancy, Reims, Clermont-Ferrand and Saint-Antoine hospitals in Paris) were enrolled in the study. Data were collected from 1 September 2019 (5 months before the outbreak of the epidemic in France, so that all enrolled patients had been exposed to a biologic prior to the start of the epidemic) to 1 January 2021.3 In each centre, we obtained the list of all patients receiving intravenous biological agents from the hospital pharmacist. Therefore, all patients receiving one of the four drugs within the time frame of the study were enrolled in each centre. The occurrence of hospitalised COVID-19 was the primary outcome criterion, that is, SARS-CoV-2 presence confirmed by PCR and resulting in hospitalisation or death. Data were analysed with Bayesian methods in univariate and multivariate analyses …

Immune-checkpoint inhibitors (ICI) have revolutionized cancer therapy but are associated with infrequent but lethal myocarditis, for which management remains uncertain. Abatacept, a CTLA-4 fusion protein targeting CD86 on antigen presenting cells and leading to global T-cell anergy, has been described as a potential treatment in individual reports. Yet, abatacept treatment dosage, schedule and optimal combination with other immunosuppressive therapies are unclear. We describe a 25-year-old man who developed pembrolizumab (anti-PD1)-induced myocarditis 14 days after first injection for thymoma treatment, which deteriorated into cardiogenic shock, with sustained ventricular arrhythmia, requiring urgent extracorporeal life support implantation, despite prompt initiation of corticosteroids and mycophenolate-mofetil. Using a strategy of serial measurement ensuring with a target of >80% CD86 receptor occupancy on circulating monocytes, abatacept dose was adjusted and combined with ruxolitinib and methylprednisolone. This strategy resulted in high-dose of abatacept: 60 mg/kg in three doses (20 mg/kg each) within the first 10 days, followed by two doses. Clinical improvement occurred within 7 days, with resolution of systolic cardiac dysfunction, and ventricular arrhythmias resulting in successful discharge from hospital. We reversed a case of nearly lethal ICI-myocarditis, using specific patient-dose adjusted abatacept, which may serve as basis for personalized treatment of patients with severe ICI-adverse events. Trial registration number: NCT04294771.

IntroductionRandomised controlled trials (RCTs) have compared biological and targeted systemic disease-modifying antirheumatic drugs (DMARDS) against placebo in psoriatic arthritis (PsA); few have compared them head to head.ObjectivesTo compare the efficacy and safety of all evaluated DMARDs for active PsA, with a special focus on biological DMARDs (bDMARDs) licensed for PsA or psoriasis.MethodsA systematic review identified RCTs and Bayesian network meta-analysis (NMA) compared treatments on efficacy (American College of Rheumatology (ACR) response, Psoriasis Area and Severity Index (PASI) response, resolution of enthesitis and dactylitis) and safety (patients discontinuing due to adverse events (DAE)) outcomes. Subgroup analyses explored ACR response among patients with and without prior biological therapy exposure.ResultsThe NMA included 46 studies. Results indicate that some tumour necrosis factor inhibitors (anti-TNFs) may perform numerically, but not significantly, better than interleukin (IL) inhibitors on ACR response but perform worse on PASI response. Few significant differences between bDMARDs on ACR response were observed after subgrouping for prior bDMARD exposure. Guselkumab and IL-17A or IL-17RA inhibitors—brodalumab, ixekizumab, secukinumab—were best on PASI response. These IL-inhibitors and adalimumab were similarly efficacious on resolution of enthesitis and dactylitis. Infliximab with and without methotrexate, certolizumab 400 mg every 4 weeks and tildrakizumab showed the highest rates of DAE; abatacept, golimumab and the IL-inhibitors, the lowest.ConclusionsDespite similar efficacy for ACR response, IL-17A and IL-17RA inhibitors and guselkumab offered preferential efficacy to anti-TNFs in skin manifestations, and for enthesitis and dactylitis, thereby supporting drug selection based on predominant clinical phenotype.

Background:Rheumatoid arthritis (RA) is a common chronic autoimmune disease. Abatacept (CTLA4-immunoglobulin) is one of the biological disease-modifying antirheumatic drug (bDMARD) for RA patients with indequate response to methotrexate. Recently, Yokoyama-Kokuryo et al. compared gene expression levels between abatacept responders and non-responders in RA patients using a microarray and found that type I IFN score and expression levels of nine genes may be used as a biomarker to predict response to abatacept. However, little study used RNA sequencing (RNA-seq) to identify whole blood gene expression signatures to predict therapeutic response to abatacept.Objectives:The aim of this study is to identify gene expression signatures to predict therapeutic responses to abatacept in RA patients using RNA-seq.Methods:This study is a single-center, prospective study. We used a PAX gene Blood RNA kit to collect whole blood at baseline and 4 weeks after abatacept treatment from RA patients. We also measured DAS28, physician global assessment, HAQ, ESR, CRP at baseline and 12 week to calculate EULAR response at 12 week. Patients with good EULAR response were defined as responders and those with moderate or no EULAR response were defined as non-responders.Results:We finally conducted RNA-seq for whole blood from 7 RA patients initiating abatacept therapy. Of the 7 RA patients, one was non-responder and 6 were responders. We first use DESeq2 to analyze the differentially expressed genes of non-responder and responder before taking the drug. We used hierarchical clustering and PCA to evaluate the overall similarity of the samples, and group the patient data, and find that the nonresponder can be distinguished from responders. Subsequently, we analyzed the differentially expressed genes of the two groups of non-responder and responder patients before taking the drug. Before treatment, we found that 72 genes had a higher expression in the non-responder, and 23 genes had a higher expression level in responders. Figure 1 showed the top 20 DEG Heatmap between the non-responder and responders.Using these two sets of genes for GO analysis, we found that most of the pathways in the non-responder are related to immune response and cytokine production, and most of the pathways in the responders are related to antigen processing and MHC class II.Figure 1.Top 20 DEG Heatmap between non-responder and respondersConclusion:The study showed that most of the pathways in RA patients with no EULAR response to abatacept are related to immune response and cytokine production; while most of the pathways in RA patients with moderate/good response to abatacept are related to antigen processing and MHC class II.References:[1]Yokoyama-Kokuyo W, Yamazaki H, Takeuchi T, et al. Identification of molecules associated with response to abatacept in patients with rheumatoid arthritis. Arthritis Research & Therapy. 2020;22:46.Disclosure of Interests:Hsin-Hua Chen Grant/research support from: This is an investigator-sponsored trial with Bristol-Myers Squibb who provides funding support., Wen-Cheng Chao: None declared, Jing-Rong Wang: None declared, Tai-Ming Ko: None declared

Background:The calcium-binding proteins S100A8/A9 (calprotectin) and S100A12 (extracellular newly identified receptor for advanced glycation end-products binding protein [EN-RAGE]) are involved in multiple signalling pathways to mediate inflammation, can be secreted by activated monocytes/macrophages and exhibit cytokine-like extracellular functions. Circulating levels of these proteins have been associated with disease and clinical responses in systemic juvenile idiopathic arthritis (sJIA), including treatment response.1 Studies suggest that serum S100A8/A9 and S100A12, which are released at inflammation sites, are more specific biomarkers of local inflammation (e.g. in the synovium) than systemic biomarkers such as CRP and ESR.2,3Objectives:To investigate if baseline S100A8/A9 and S100A12 predict clinical response to abatacept treatment in polyarticular JIA (pJIA), and to assess whether changes from baseline in S100A8/A9 or S100A12 can be better prognostic markers for response to abatacept treatment than CRP in pJIA.Methods:Data are from a phase III trial of SC abatacept for the treatment of pJIA (NCT01844518).4 This 24-month, single-arm, open-label, international, multicentre, two-part study included male and female patients with pJIA aged 2–17 years. This analysis examined the correlation between biomarkers (S100A8/A9, S100A12 and high-sensitivity CRP [hsCRP]) and disease activity (measured using Juvenile Arthritis Disease Activity Score [JADAS]) at baseline, baseline biomarker values as predictors of future treatment response (ACR and JADAS endpoints), and the correlation between change from baseline in biomarker values and treatment response at Day 113.Results:Of 219 total patients, 158 (72%) had S100A8/A9 values and 155 (71%) had S100A12 values at baseline. Median S100A8/A9 and S100A12 values were 3295 ng/mL (normal range, 716–3004 ng/mL) and 176 ng/mL (normal range, 32–385 ng/mL), respectively. S100A8/A9, S100A12 and hsCRP (median 0.20 mg/dL; normal ≤0.6 mg/dL) had a low-to-moderate but significant association with disease activity at baseline; coefficients for associations between JADAS71-CRP low disease activity (LDA) and the biomarkers S100A8/A9, S100A12 and hsCRP were 0.23 (p=0.0038), 0.16 (p=0.0448) and 0.26 (p=0.0001), respectively. Baseline S100A8/A9 level above the median was associated with lower odds of ACR100 at Day 113 (p=0.0052). Figure 1 shows the associations of baseline biomarker values with Day 113 ACR and JADAS scores in the overall population. Baseline S100A8/A9 or S100A12 did not significantly influence ACR50 or ACR70 responses at Day 113, but high baseline values were associated with reduced odds of ACR90 (p=0.01), ACR100 (p=0.005), ACR-inactive disease (ID) (p=0.0001), and JADAS71-CRP (LDA) (p=0.02). By Day 477, elevated baseline S100A12 was still significantly associated with lower odds of ACR100 overall (0.467; p=0.0248) but baseline S100A8/A9 was not; at Day 645, neither was significantly associated with ACR100 response. At Day 113, changes from baseline in S100A8/A9 and S100A12 were correlated with ACR100 (coefficients of 0.22 [p=0.0082] and 0.26 [p=0.0015], respectively) and with ACR-ID (0.22 [p=0.0067] and 0.26 [p=0.0014], respectively); change in hsCRP was not significantly correlated with disease response.Conclusion:S100A8/A9 and S100A12 may serve as prognostic biomarkers to predict response to abatacept treatment at Day 113. Changes from baseline S100A8/A9 and S100A12 levels were more highly correlated with efficacy outcomes including ACR100 and ACR-ID at Day 113 compared with hsCRP.References:[1]Aljaberi N, et al. Pediatr Rheumatol Online J 2020;18:7.[2]Hammer H, et al. Arthritis Res Ther 2011;13:R178.[3]Nordal HH, et al. BMC Musculoskelet Disord 2014;15:335.[4]Brunner H, et al. Arthritis Rheumatol 2018;70:1144–1154.Acknowledgements:Professional medical writing and editorial assistance was provided by Rob Coover, MPH, at Caudex and was funded by Bristol Myers Squibb.Disclosure of Interests:Nicolino Ruperto Speakers bureau: NR has received honoraria for consultancies or speaker bureaus (< 10.000 USD each) from the following pharmaceutical companies in the past 3 years: Ablynx, Astrazeneca-Medimmune, Bayer, Biogen, Boehringer, Bristol Myers Squibb, Celgene, Eli Lilly, EMD Serono, GlaxoSmithKline, Hoffmann-La Roche, Janssen, Merck, Novartis, Pfizer, R-Pharma, Sinergie, Sobi and UCB, Consultant of: NR has received honoraria for consultancies or speaker bureaus (< 10.000 USD each) from the following pharmaceutical companies in the past 3 years: Ablynx, Astrazeneca-Medimmune, Bayer, Biogen, Boehringer, Bristol Myers Squibb, Celgene, Eli Lilly, EMD Serono, GlaxoSmithKline, Hoffmann-La Roche, Janssen, Merck, Novartis, Pfizer, R-Pharma, Sinergie, Sobi and UCB, Grant/research support from: The IRCCS Istituto Giannina Gaslini (IGG), where NR works as full-time public employee has received contributions (>10.000 USD each) from the following industries in the last 3 years: Bristol Myers Squibb, Eli Lilly, F Hoffmann-La Roche, GlaxoSmithKline, Janssen, Novartis, Pfizer, Sobi. This funding has been reinvested for the research activities of the hospital in a fully independent manner, without any commitment with third parties., Grant Schulert Speakers bureau: Novartis, Consultant of: SOBI, Alyssa Sproles: None declared, Sherry Thornton: None declared, Gabriel Vega Cornejo Speakers bureau: AbbVie, Grant/research support from: Bristol Myers Squibb, Eli Lilly, Janssen, Parexel, Sanofi, Jordi Anton Speakers bureau: AbbVie, Gebro, GlaxoSmithKline, Novartis, Pfizer, Roche, Sobi, Consultant of: AbbVie, Gebro, GlaxoSmithKline, Novartis, Pfizer, Roche, Sobi, Grant/research support from: AbbVie, Amgen, Gebro, GlaxoSmithKline, Lilly, Novartis, Novimmune, Pfizer, Roche, Sanofi, Sobi, Ruben Cuttica Speakers bureau: AbbVie, Bristol Myers Squibb, GlaxoSmithKline, Lilly, Novartis, Pfizer, Roche, UCB, Paid instructor for: AbbVie, Novartis, Pfizer, Roche, Consultant of: AbbVie, Bristol Myers Squibb, GlaxoSmithKline, Lilly, Novartis, Pfizer, Roche, UCB, Michael Henrickson: None declared, Ivan Foeldvari Consultant of: Bristol Myers Squibb, Gilead, Hexal, MEDAC, Novartis, Pfizer, Sanofi, Daniel Kingsbury Consultant of: Pfizer, Margarita Askelson Consultant of: Currently working for Syneos Health providing services to Bristol Myers Squibb, Jinqi Liu Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Sumanta Mukherjee Shareholder of: Bristol Myers Squibb, GlaxoSmithKline, Employee of: Bristol Myers Squibb, GlaxoSmithKline, Robert Wong Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Daniel J Lovell Speakers bureau: Genentech, Wyeth Pharm, Consultant of: Abbott, Amgen, AstraZeneca, Boehringer Ingelheim, Celgene, GlaxoSmithKline, Hoffman-La Roche, Novartis, Pfizer, Regeneron, Takeda, UBC, Wyeth Pharma, Xoma, Alberto Martini Speakers bureau: AbbVie, Novartis, Consultant of: AbbVie, Eli Lilly, EMD Serono, Idorsia, Janssen, Novartis, Pfizer, Alexei Grom Consultant of: AB2Bio, Novartis, Sobi (NovImmune), Grant/research support from: AB2Bio, Novartis, Sobi (NovImmune), Hermine Brunner Speakers bureau: GlaxoSmithKline, Novartis, Pfizer, Roche, Paid instructor for: Novartis, Pfizer (funds go to CCHMC/employer), Consultant of: Boehringer Ingelheim, Bristol Myers Squibb, GlaxoSmithKline, Janssen, Merck, Novartis, Pfizer, Roche, UCB (funds go to CCHMC/employer), Grant/research support from: Bristol Myers Squibb, Pfizer (funds go to CCHMC/employer).

Background:In the ACTION (NCT02109666) study, multivariable Cox proportional hazards regression models showed that the predictors of 1-year retention to abatacept treatment were: patient global pain assessment, country, reason for stopping last biologic, number of prior biologic treatments, abatacept monotherapy, RF/anti-cyclic citrullinated peptide (CCP) status, previous neoplasms, psychiatric disorders and cardiac disorders.1 Machine learning techniques, using the gradient-boosting model, subsequently identified additional predictors of abatacept retention in patients with moderate-to-severe RA enrolled in ACTION; however, the analysis did not show the directionality of the predictors.2Objectives:To improve the clinical interpretability of the machine learning model in terms of directionality and the importance of each variable in predicting retention.Methods:Previous analyses using the gradient-boosting model to identify predictors of abatacept retention at 1 year in the ACTION study have been described.2 This analysis used SHapley Additive exPlanations (SHAP), a mathematical framework, to show how a particular predictor value influences prediction in the context of all other predictors. Higher SHAP values indicate a higher likelihood of retention. The contribution of every variable in the model’s prediction (with the exception of country variables) was computed for each data point to capture individual variable impact. This enabled interpretation for level of importance and directionality at a patient level.Results:Using data from 2350 patients enrolled in ACTION (May 2008 to December 2013), the mean retention rate at 1 year was 59.3% (n=1393). Overall variable importance is shown in Figure 1. After removal of country variables, the top five baseline predictors of retention were: no previous corticosteroid use, ACR functional class II, ≥2 prior biologic treatments prior to abatacept initiation, abatacept monotherapy and HAQ-DI. In terms of directionality, no previous corticosteroid use, ≥2 prior biologic treatments prior to abatacept initiation, abatacept monotherapy and a higher HAQ-DI score at baseline were associated with a lower likelihood of retention; ACR functional class II was associated with a higher likelihood of retention.Conclusion:The gradient-boosting model previously identified predictors of abatacept retention from ACTION;2 the addition of SHAP in this analysis has provided information on the importance and directionality of those predictors. The most important predictor of abatacept retention was no previous corticosteroid use, which was associated with lower retention. The models and predictors identified could be further refined by using additional datasets from clinical trials. Machine learning offers an innovative and complementary approach to biostatistics and could be used to identify treatment response predictors at an individual patient level, leading to a more personalised treatment approach.References:[1]Alten R, et al. RMD Open 2017;3:e000538.[2]Alten R, et al. Presented at the virtual ACR Convergence 2020; 5–9 November 2020. Poster number 1745.Acknowledgements:This study was supported by Bristol Myers Squibb. Professional medical writing and editorial assistance was provided by Claire Line, PhD, at Caudex and was funded by Bristol Myers Squibb.Disclosure of Interests:Rieke Alten Speakers bureau: AbbVie, Bristol Myers Squibb, Gilead, Janssen, Lilly, Pfizer, Consultant of: AbbVie, Bristol Myers Squibb, Gilead, Janssen, Lilly, Pfizer, Grant/research support from: AbbVie, Bristol Myers Squibb, Gilead, Janssen, Lilly, Pfizer, Claire Behar Shareholder of: I have not invested directly in pharmaceutical companies producing drugs/devices for use in rheumatology however I may have shares via the funds linked to my life insurance., Consultant of: Bristol Myers Squibb, Christine Boileau Consultant of: AstraZeneca, Bristol Myers Squibb, Nanobiotix, Pierre Merckaert Consultant of: Bristol Myers Squibb, Ebenezer Afari Consultant of: Bristol Myers Squibb, Virginie Vannier-Moreau Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Sean Connolly Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Aurelie Najm Speakers bureau: Bristol Myers Squibb, Consultant of: Bristol Myers Squibb, Pierre-Antoine Juge Consultant of: Bristol Myers Squibb, Angshu Rai Shareholder of: Amgen Inc, Consultant of: Amgen Inc, Employee of: Amgen Inc, Bristol Myers Squibb, Yedid Elbez Consultant of: Bristol Myers Squibb, Karissa Lozenski Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb

Background:Biologic and target synthetic disease modifying anti-rheumatic drugs (bDMARDs and tcDMARDs) are recommended to control RA disease activity, pain and steroid use. Following randomized clinical trials (RCTs) and their post-hoc analyses, the Janus Kinase Inhibitor tsDMARDs BARI was superior to reference bDMARD Adalimumab in reducing disease activity, pain and functional disability. In addition, BARI monotherapy also determined more significant pain reduction and functional improvement when compared to Tocilizumab monotherapy (3).Objectives:to confirm RCT results in a real-life clinical setting, with focus on disease activity, pain, functional disability and steroid tapering, when comparing BARI to bDMARDs for the treatment of active RA.Methods:RA patients starting BARI or a bDMARD for active RA were retrospectively evaluated from June 2019 to June 2020. Disease activity (DAS28CRP, SDAI, CDAI), pain visual analogic scale (pain_VAS), functional disability (HAQ) assessments and mean prednisone dosage (pred_dose) were collected at baseline (BL), 3 months (3M) and 6 months (6M) after BARI/bDMARD initiation. The changes of the outcome measures were evaluated between BL-3M, 3M-6M and BL-6M, as well as between BARI and bDMARDs groups. Finally, we assessed the variables associated with prednisone tapering in the whole population.Results:90 out of 100 RA patients evaluated (baseline: age 57±12 years, disease duration 131±100 months, DAS28PCR 4.8±1.0, pain_VAS 61±23 mm, prednisone dose 5.5±5.3 mg) were eligible for the study; 49 received BARI and 41 bDMARDs (17 abatacept, 12 TNF inhibitors, 11 tocilizumab, 1 rituximab). At BL, the two groups did not differ statistically in terms of age, sex, disease duration, disease activity, pain_VAS, previous bDMARD failure or ts/bDMARD naive, concomitant conventional synthetic DMARDs treatment, pred_dose. Both BARI and bDMARDs determined a significant reduction in activity scales and HAQ when comparing BL-3M and BL-6M, with only pain_VAS and pred_dose showing a significant decrease in the 3M-6M interval. When comparing the two groups, BARI showed a significantly higher reduction of pred_dose (-3.2±5.1 vs -1.7±3.7 mg at BL-3M, and -4.1±5.3 vs -1.9±4.6 mg at BL-6M), which was not significant after adjusting for BL pred_dose. No other difference was seen when the two groups, including the numerically higher reduction of pain_VAS in the BARI group (-29±28 vs -20±27 mm at BL-3M and -35±25 vs -30±28 mm at BL-6M comparison). The analysis of the predictors for steroid tapering (Δmean_pred) in the two intervals, showed that BL DAS28PCR, DAS28PCR BL-3M change and BL pred_dose were associated with BL-3M Δmean_pred, while 3M pain_VAS and 3M pred_dose were associated with 3M-6M Δmean_pred.Conclusion:Although limited by the small samples and the retrospective nature, our real-life comparison shows similar efficacy of BARI and bDMARDs in terms of disease activity control, functional disability and pain. In addition, the treatment with BARI or bDMARD did not influence the steroid tapering, which was driven mostly by its initial dose, disease activity and pain. Larger real-life multi-center studies are warranted to confirm our results.References:[1]Taylor PC et al. Baricitinib versus Placebo or Adalimumab in Rheumatoid Arthritis. N Engl J Med. 2017 Feb 16;376(7):652-662.[2]Fautrel B et al. Effect of Baricitinib and Adalimumab in Reducing Pain and Improving Function in Patients with Rheumatoid Arthritis in Low Disease Activity: Exploratory Analyses from RA-BEAM. J Clin Med. 2019 Sep 5;8(9):1394.[3]Fautrel B et al. Comparative effectiveness of improvement in pain and physical function for baricitinib versus adalimumab, tocilizumab and tofacitinib monotherapies in rheumatoid arthritis patients who are naïve to treatment withDisclosure of Interests:Laura Cometi: None declared, Cosimo Bruni Speakers bureau: Actelion, Consultant of: Eli Lilly, Grant/research support from: Fondazione Italiana Ricerca sull’Artrite (FIRA), Gruppo Italiano lotta alla Sclerodermia (GILS), New Horizon Fellowship, European Scleroderma Trials and Research (EUSTAR) group, Foundation for Research in Rheumatology (FOREUM)., Lorenzo Tofani: None declared, Giulia Tesei: None declared, Francesca Nacci: None declared, Ginevra Fiori: None declared, Francesca Bartoli: None declared, Marco Matucci-Cerinic Speakers bureau: Biogen Italia, Actelion, Bayer, Boehringer Ingelheim, CSL Behring, Eli-Lilly, Consultant of: Biogen Italia, Actelion, Bayer, Boehringer Ingelheim, CSL Behring, Eli-Lilly, Grant/research support from: Biogen Italia, Actelion, Bayer, Boehringer Ingelheim, CSL Behring, Eli-Lilly

Background:Interstitial lung disease (ILD) is a severe complication of Rheumatoid Arthritis (RA). Usual interstitial pneumonia (UIP) is considered to be more frequent and severe in RA than non-specific interstitial pneumonia (NSIP). Abatacept (ABA) and Rituximab have demonstrated efficacy in RA-ILD [1-3].Objectives:To compare the efficacy of ABA in RA-ILD patients according to radiological patterns of UIP or NSIP.Methods:From an observational multicenter study of 263 RA-ILD patients treated with ABA, we selected those with UIP or NSIP [2]. We analyzed in the 2 groups from baseline up to 24 months the following outcomes: a) Forced Vital Capacity (FVC), b) Carbon monoxide diffusing capacity (DLCO), c) Chest High Resolution Computed Tomography (HRCT), and d) dyspnea. Differences between final follow-up and basal visit were calculated as the average difference and 95% Confidence Interval (95% CI). Multivariable linear regression was used to assess the differences between the 2 groups.Results:We studied 190 patients with UIP (n=106) and NSIP (n=84). Patients with UIP were older, had more positivity for rheumatoid factor and had received more sulfasalazine (Table 1). ILD duration up to ABA initiation was relatively short in both groups, with a median [IQR] of 16 [4-50] and 11 [2-36] months in UIP and NSIP patterns, respectively. Mean baseline values of FVC and DLCO were > 80% and > 60%, respectively, in the 2 groups, with a lower FVC in UIP (82% vs 89% in NSIP, pConclusion:ABA seems to be equally effective in stabilizing of DLCO, FVC and HRCT in UIP and NSIP in RA-ILD. Our results suggest that an early administration of ABA in ILD, before significant structural lung damage development, may be preferable to prevent interstitial progression, regardless of the radiological pattern.References:[1]Fernández-Díaz C, et al. Semin Arthritis Rheum. 2018 Aug;48(1):22-27. doi: 10.1016/j.semarthrit.2017.12.012[2]Fernández-Díaz C, et al. Rheumatology (Oxford). 2020 Dec 1;59(12):3906-3916. doi: 10.1093/rheumatology/keaa621[3]Atienza-Mateo B, et al. J Clin Med. 2020 Sep 23;9(10):3070. doi: 10.3390/jcm9103070Table 1.Main general features at baseline.UIP (n=106)NSIP (n=84)p valueAge, years mean±SD66±1063±100.049Women, n (%)59 (56)49 (58)0.71Smoker ever, n (%)51 (48)45 (54)0.46ILD duration up toABA, months, median [IQR]16 [4-50]11 [2-36]0.57RF100 (94)71 (85)0.041ACPA, n (%)96 (91)75 (89)0.83FVC (% of the predicted), mean±SD82±2189 ±190.025DLCO (% of the predicted), mean±SD63 ±1965 ±160.46ABA monotherapy, n (%)45 (42)41 (49)0.38ABA combined+ MTX // + other cDMARD, n (%)15 (14) // 46 (43)16 (19) // 27 (32)0.17Prednisone at baseline, mg/day, median [IQR]7.5 [5-10]10 [5-10]0.20Previous immunosuppressive therapy, n (%)MTX81 (76)68 (81)0.45Leflunomide48 (45)31 (37)0.25Sulfasalazine16 (15)5 (6)0.046Hydroxychloroquine24 (23)16 (19)0.55Anti-TNF drugs37 (35)30 (36)0.80Rituximab19 (18)15 (18)0.99Tocilizumab12 (11)12 (14)0.54ABA, abatacept; ACPA, anti-citrullinated protein antibodies; DMARD, disease-modifying antirheumatic drug, ILD, Interstitial lung disease; MTX, methotrexate; NSIP, non-specific interstitial pneumonia; RA, rheumatoid arthritis; TNF, tumor necrosis factor; UIP, usual interstitial pneumonia.Figure 1.Evolution of pulmonary function tests in RA-ILD patients with UIP and NSIP patterns. FVC and DLCO are expressed as mean (95%CI) and compared between the 2 groups.Acknowledgements:the Spanish Collaborative Group of Abatacept in Interstitial Lung Disease Associated with Rheumatoid ArthritisDisclosure of Interests:Belén Atienza-Mateo: None declared, Carlos Fernández-Díaz Speakers bureau: Brystol Myers Squibb, Santos Castañeda: None declared, Rafael Melero: None declared, FRANCISCO ORTIZ SANJUAN: None declared, Ivette Casafont-Solé: None declared, Sebastián C Rodriguez-García: None declared, Iván Ferraz-Amaro: None declared, Miguel A González-Gay: None declared, Ricardo Blanco Speakers bureau: Brystol Myers Squibb

Background:Since tofacitnib is a tsDMARD with a different mechanism of action compared to bDMARDs, along with the fact that recent releases of bDMARDs or tsDMARDs have led to numerous possible switching patterns, there is a need for comparative studies of bDMARDs and tofacitinib with subsequent drug survival among RA patients.Objectives:To determine the association of first, second, and third-line biologic disease- modifying antirheumatic drugs (bDMARDs) and tofacitinib with drug survival among rheumatoid arthritis (RA) patients.Methods:The study population was composed of 8,018 seropositive RA patients who were prescribed bDMARDs or tofacitinib between January 2014 and January 2019 from the Korean Health Insurance Review and Assessment Service database. First, second, and third-line choice of tumor necrosis factor inhibitors (TNFi) including etanercept, infliximab, adalimumab, and golimumab, as well as non-TNFi including tocilizumab, rituximab, tofacitinib, and abatacept were assessed. Multivariate Cox proportional hazards regression was used to determine the adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for drug failure according to bDMARD or tofacitinib choice starting from the initial prescription date.Results:Compared to first etanercept users, patients with first tocilizumab (aHR 0.56, 95% CI 0.46-0.68), tofacitinib (aHR 0.27, 95% CI 0.18-0.42), or abatacept (aHR 0.83, 95% CI 0.69- 0.99) had lower risk of drug failure. Second choice of tocilizumab (aHR 0.38, 95% CI 0.25- 0.55), tofacitinib (aHR 0.23, 95% CI 0.15-0.37), or abatacept (aHR 0.54, 95% CI 0.35-0.84) was associated with lower drug failure risk compared to second etanercept users. Finally, third choice of tocilizumab (aHR 0.32, 95% CI 0.16-0.62) or tofacitinib (aHR 0.35, 95% CI 0.19- 0.63) was associated with lower drug failure risk compared to third TNFi users.Conclusion:First and second-line tocilizumab, tofacitinib, or abatacept may lead to improved drug survival. Third choices of tocilizumab or tofacitinib may be beneficiary in reducing drug failure risk among RA patients.References:[1].Neovius M, Arkema EV, Olsson H, et al. Drug survival on TNF inhibitors in patients with rheumatoid arthritis comparison of adalimumab, etanercept and infliximab. Ann Rheum Dis 2015;74(2):354-60.Table 1.Risk of drug failure on rheumatoid arthritis patients according to first, second, and third choice of bDMARD or tofacitinib.EventsPerson-yearsIncidenceaHR95% CIFirst-line choice (n=8,018) Etanercept2902,3961211.00reference Infliximab2361,4171671.361.14-1.62 Adalimumab4492,7181651.281.10-1.48 Golimumab2581,9551321.060.90-1.26 Tocilizumab1712,623650.560.46-0.68 Rituximab129340.290.04-2.08 Tofacatinib24502480.270.18-0.42 Abatacept2162,207980.830.69-0.99Second-line choice (n=1,645) Etanercept411512721.00reference Infliximab16513141.040.58-1.88 Adalimumab852753091.070.72-1.60 Golimumab412042010.790.51-1.23 Tocilizumab85918930.380.25-0.55 Rituximab4311290.520.18-1.46 Tofacatinib35484720.230.15-0.37 Abatacept462991540.540.35-0.84Third-line choice (n=353) Etanercept3191581.00reference Infliximab5105001.270.27-5.91 Adalimumab5172940.990.22-4.38 Golimumab13225912.230.60-8.25 Tocilizumab171271340.470.13-1.68 Rituximab3221360.600.12-3.09 Tofacatinib231621420.500.14-1.77 Abatacept17592881.110.31-3.96Adjusted hazard ratios calculated by multivariate Cox proportional hazards regression after adjustments for age, sex, hospital type, number of csDMARDs, first bDMARDs or tofacitinib for second and third-line choice analysis, Charlson comorbidity index, and enrollment year.Incidence calculated as the number of events per 1,000 person-years.Acronyms: aHR, adjusted hazard ratio; CI, confidence interval.Disclosure of Interests:Byeongzu Ghang: None declared, Seulggie Choi: None declared, Eun Young Lee Grant/research support from: This work was supported by grants from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute, funded by the Ministry of Health and Welfare, Republic of Korea [HI14C1277] and Britol-Myers Squibb [IM101-735].

Background:RA is more responsive to treatment in the early stages of disease, and early treatment may lead to better long-term outcomes.1,2 Data on the effectiveness of specific drugs as first or later lines of therapy will help inform treatment sequencing.Objectives:Data from patients enrolled in the Corrona RA Registry were used to compare the effectiveness of abatacept across lines of therapy overall (primary cohort) and in a subset of patients who were anti-citrullinated protein antibody positive (ACPA+).Methods:Patients with RA who initiated abatacept (January 2006 to October 2020), had 6 months’ follow-up (within 4−9 months of starting abatacept), had baseline (BL) and follow-up CDAI scores available, and had BL CDAI >2.8 were included. Outcomes were compared for first-, second- and third or higher-line therapy: 0, 1 or ≥2 prior biologic DMARDs or Janus kinase inhibitors, respectively. Continuous outcomes included change from BL to 6 months in mean CDAI and patient-reported pain, fatigue, and HAQ. Binary outcomes included rate of achieving minimal clinically important difference (MCID) in CDAI or modified ACR20/50/70 at 6 months. Continuous and binary outcomes were analysed using multiple linear and logistic regression, respectively. The models included line of therapy, age, sex, disease duration, work status, SC nodules, history of hypertension and depression, BL CDAI, BL patient-reported pain and BL fatigue. Additional subgroup analyses were carried out in patients with moderate/high disease activity (CDAI >10) at BL.Results:In total, 2876 patients (2327 with BL CDAI >10; 890 ACPA+) were included; 442, 911, and 1523 patients initiated first-, second- or third/higher-line abatacept, respectively. Compared with patients on second/third/higher-line abatacept therapy, those on first-line abatacept were significantly older, had shorter disease duration, and had lower BL CDAI, pain and fatigue (all pConclusion:There were significant differences in improvement in clinical disease activity and patient-reported outcomes across lines of therapy. Better treatment responses were observed with earlier lines of abatacept therapy in the overall population, in patients who were ACPA+ and in those with moderate/high BL disease activity.References:[1]Harrold LR, et al. Clin Rheumatol 2017;36:1215−1220.[2]Monti S, et al. RMD Open 2015;1(Suppl 1):e000057.Table 1.Adjusted mean change in CDAI and patient-reported outcomes from BL to 6 months after initiation of abatacept by line of therapy (primary cohort)Adjusted outcome, mean change (SE)First-line (n=440)Second-line (n=898)Third/higher-line (n=1515)p valueaCDAI−7.96 (0.33)−7.49 (0.27)−5.74 (0.19)Patient-reported pain (VAS 0–100)−9.43 (0.69)−7.98 (0.47)−7.70 (0.35)0.074Patient-reported fatigue (VAS 0–100)−7.49 (0.71)−5.87 (0.51)−4.81 (0.36)0.002Patient-reported HAQ−0.16 (0.01)−0.12 (0.01)−0.08 (0.01)aEstimated by multiple linear regression model adjusted for age, sex, disease duration, work status, SC nodules, history of hypertension and depression, BL CDAI, BL patient-reported pain and BL fatigue (factors that were identified a priori based on clinical experience or that differed significantly by line of therapy); p values reflect ANOVA overall test of differences across lines of therapy.VAS=visual analogue scale.Acknowledgements:Professional medical writing and editorial assistance was provided by Claire Line, PhD, at Caudex and was funded by Bristol Myers Squibb. The poster was a collaborative effort between Corrona and Bristol Myers Squibb, with financial support provided by Bristol Myers Squibb. This study was sponsored by Corrona, LLC. Corrona is supported through contracted subscriptions with multiple pharmaceutical companies.Disclosure of Interests:Leslie Harrold Consultant of: AbbVie, Bristol Myers Squibb, Genentech/Roche, Grant/research support from: Pfizer, Keith Wittstock Employee of: Bristol Myers Squibb, Sheila Kelly Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Sang Hee Park Employee of: Bristol Myers Squibb, Xue Han Employee of: Bristol Myers Squibb, Ying Shan: None declared, Carla Roberts-Toler: None declared, Nicole Middaugh: None declared, Vadim Khaychuk Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb

Background:Interstitial lung disease (ILD) is a severe complication of RA. Abatacept (ABA) have demonstrated efficacy in RA-ILD [1,2], although combined treatment with MTX or others DMARDs remain controversial.Objectives:To assess the efficacy and safety of ABA in monotherapy (ABAMONO) versus combined-ABA, ABA plus MTX(ABAMTX) or ABA plus other non-MTX DMARDs (ABANON-MTX), in RA-ILD.Methods:Observational multicenter study of RA-ILD caucasian patients treated with ABA. We analyzed in three groups (ABAMONO, ABAMTX, ABANON-MTX) the following outcomes: a) Dyspnea, b) FVC and DLCO, c) HRCT, d) DAS28-ESR, e) corticosteroid-sparing effect. Differences between basal and final follow-up were evaluated. Multivariable linear regression was used between the three groups.Results:We studied 263 RA-ILD patients (mean age 64.6±10 years) [ABAMONO (n=111), ABAMTX (n=46) and ABANON-MTX (n=106)]. At baseline, ABAMONO patients were older (67±10 years) and took higher prednisone dose (10 [IQR 5-15] mg/day). There was no statistically significant differences in sex, seropositivity, ILD patterns, FVC, DLCO or disease duration. In all groups, most patients experienced stabilization or improvement in FVC, DLCO, dyspnea, HRCT as well as improvement in DAS28-ESR. A statistically significant difference between basal and final follow-up was only found in corticosteroid-sparing effect in ABAMTX or ABANON-MTX(Figure 1). However, in the multivariable analysis, there were no differences in any outcome between the three groups(Table 1).Table 1.Effect in FVC, DLCO, dyspnea (mMRC) and HRCT pulmonary scan after abatacept.ABAMONON=111ABAMTXN=46ABANON-MTXN=106ABAMTXvs ABAMONOABANON-MTXvs ABAMONOpppp*UnadjustedAdjusted**UnadjustedAdjusted**Follow-up, median [IQR] months12 [6-36]12 [6-36]18[12-36]0.400.670.17Differences between basal and final follow-upFVC, %-0.5 (-2.5, 1.5)0.641.2(-0.6, 3.1)0.17-1.2 (-2.9, 0.5)0.170.330.300.390.590.90DLCO, %1.8 (-0.7, 4.34)0.160.5 (-3.8, 4.8)0.82-1.5 (-4.1, 1.1)0.260.200.580.800.070.32mMRC, n (%)Worsening5 (5)3 (8)5 (5)0.830.470.99Stable or improving93 (95)36 (92)87 (95)HRCT pulmonary scan, n (%)Worsening13 (28)2 (11)15 (25)0.240.100.78Stable or improving34 (72)19 (89)44 (75)DAS28-ESR-1.5 (-1.9, -1.0)0.000-1.2 (-1.8, -0.6)0.000-1.5 (-1.8, -1.2)0.0000.740.580.92Prednisone, mg/day-3.8 (-8.3, 0.8)0.10-2.7 (-4.6, -0.8)0.006-4.8 (-6.3, -3.4)0.0000.690.670.65Differences in DAS28-ESR, prednisone, FVC and DLCO are expressed as mean difference (95%CI) comparing final follow-up minus basal values.*Differences between the 3 groups.**Differences between ABAMTX vs. ABAMONO, and between ABANON-MTX vs ABAMONO are adjusted for age, disease duration until abatacept treatment, and DAS28 and prednisone dose at baseline.Abbreviations(DAS28-ESR: Disease activity score-erythrocyte sedimentation rate; DLCO: Carbon Monoxide Diffusing Capacity; HRCT: High resolution computed tomography; FVC: Forced vital capacity, mMRC: modified Medical Research Council scaleFigure 1.Conclusion:In caucasian individuals with RA-ILD, ABAMONO or ABAMTX or ABANON-MTX seems to be equally effective and safe. However, a corticosteroid-sparing effect is only observed in combined-ABA.References:[1]Fernández-Díaz C, et al. Abatacept in patients with rheumatoid arthritis and interstitial lung disease: A national multicenter study of 63 patients. Semin Arthritis Rheum. 2018 Aug;48(1):22-27. doi: 10.1016/j.semarthrit.2017.12.012.[2]Fernández-Díaz C, et al. Abatacept in interstitial lung disease associated with rheumatoid arthritis: national multicenter study of 263 patients. Rheumatology (Oxford). 2020 Dec 1;59(12):3906-3916. doi: 10.1093/rheumatology/keaa621.Acknowledgements:Spanish Collaborative Group of Interstitial Lung Disease Associated to Rheumatoid ArthritisDisclosure of Interests:Carlos Fernández-Díaz Speakers bureau: Roche, bristol myers squibb, Belén Atienza-Mateo: None declared, Santos Castañeda: None declared, Rafael Melero: None declared, Francisco Ortiz-Sanjuán: None declared, Ivette Casafont-Solé: None declared, J. Loricera: None declared, Sebastián C Rodriguez-García: None declared, Iván Ferraz-Amaro: None declared, Miguel A González-Gay: None declared, Ricardo Blanco Speakers bureau: bristol myers squibb

The risk of coronavirus disease 2019 (COVID-19) and disease progression among patients using immunomodulatory therapy is unclear. Accordingly, we implemented an active surveillance project with USA/Canada Infectious Disease specialists via the Emerging Infections Network (EIN) to identify COVID-19 cases occurring in patients who use immunomodulatory therapy and to describe their clinical outcomes. EIN listserv members include 2396 infectious disease physicians in the USA/Canada linked via a moderated listserv. On 8 April via listserv, we requested reports of COVID-19 cases among patients receiving immunomodulatory therapy. Two weekly reminders were later sent and case reports were collected until 22 May. We collected information regarding patient demographics, COVID-19 test results, symptoms, hospitalisation details, complications, treatment, pre-existing conditions, concomitant therapies, and patient outcomes. We conducted descriptive analyses of these patient factors and compared differences between survivors and non-survivors. We grouped immunosuppressive therapies by class (table 1). View this table: Table 1 COVID-19 outcomes among autoimmune patients receiving immunomodulatory therapy Thirty-eight physicians screened over 2500 COVID-19 cases from which 77 (3%) were identified using immunomodulatory drugs. Of these, 52% were female, median age of 60 years (range, 16–84) and 83.1% had autoimmune disease (rheumatoid arthritis (19, 24.7%), ulcerative colitis (5, 6.5%) and sarcoidosis (5, 6.5%) were most common). Comorbidities included hypertension (26, 33.8%), diabetes (19, 24.7%), underlying chronic kidney disease (11, 14.3%) and others. All patients had PCR-confirmed COVID-19. Symptoms included dyspnoea (70.1%), fever (68.8%) and cough (64.9%). At time of COVID-19 diagnosis, 31 (40%) were using biologic therapies including anti tumor necrosis factor (anti-TNF) therapies (n=16), rituximab (n=6), abatacept (n=2), tocilizumab (n=2) and other (n=5). Among those using non-biologics at baseline (46, 60%), the following therapies were in use: janus kinase (JAK) inhibitors (3, 6.5%), non-biologic disease-modifying antirheumatic drugs (DMARDs) (11, 24%), prednisone alone (5, 11%) or other (27, 59%). Among …

ObjectivesTo study the effects of abatacept on disease activity and on muscle biopsy features of adult patients with dermatomyositis (DM) or polymyositis (PM).MethodsTwenty patients with DM (n=9) or PM (n=11) with refractory disease were enrolled in a randomised treatment delayed-start trial to receive either immediate active treatment with intravenous abatacept or a 3 month delayed-start. The primary endpoint was number of responders, defined by the International Myositis Assessment and Clinical Studies Group definition of improvement (DOI), after 6 months of treatment. Secondary endpoints included number of responders in the early treatment arm compared with the delayed treatment arm at 3 months. Repeated muscle biopsies were investigated for cellular markers and cytokines.Results8/19 patients included in the analyses achieved the DOI at 6 months. At 3 months of study, five (50%) patients were responders after active treatment but only one (11%) patient in the delayed treatment arm. Eight adverse events (AEs) were regarded as related to the drug, four mild and four moderate, and three serious AEs, none related to the drug. There was a significant increase in regulatory T cells (Tregs), whereas other markers were unchanged in repeated muscle biopsies.ConclusionsIn this pilot study, treatment of patients with DM and PM with abatacept resulted in lower disease activity in nearly half of the patients. In patients with repeat muscle biopsies, an increased frequency of Foxp3+ Tregs suggests a positive effect of treatment in muscle tissue.

We read with great interest the Global Rheumatology Alliance report on COVID-19 on biologic or targeted synthetic disease-modifying antirheumatic drugs (DMARDs) in rheumatoid arthritis (RA).1 The first important result of the registry database is that B-cell depletion, by compromising the primary antibody response, increases the severity of infected patients. Considering the critical role of B cells in the adaptive immune response, this sounds quite correct.2 Even the data on interleukin 6 and tumour necrosis factor (TNF) inhibitors appear quite understandable considering the systemic inflammation raised by SARS-CoV-2 infection, the results of the Randomised Embedded Multifactorial Adaptive Platform for Community-acquired Pneumonia (REMAP-CAP) trial in patients on National Institute of Allergy and Infectious Diseases ordinal scale (NIAID)-Ordinal Scale 6 and 73 and the demonstrated role of TNF–TNF receptor 1 in inducing lymphopenia and T-cell dysfunction in severe–critical disease.4 Importantly, the death rate in abatacept was found close to that in JAK inhibitors. …

ObjectiveTo explore possible associations of treatment with biological disease-modifying antirheumatic drugs (bDMARDs), including T-cell-based and interleukin-6 inhibition (IL-6i)-based therapies, and the risk for type 2 diabetes mellitus (T2DM) in patients with rheumatoid arthritis (RA).Study design, setting and participantsFive treatment groups were selected from a United States Electronic Medical Records database of 283 756 patients with RA (mean follow-up, 5 years): never received bDMARD (No bDMARD, n=125 337), tumour necrosis factor inhibitors (TNFi, n=34 873), IL-6i (n=1884), T-cell inhibitors (n=5935) and IL-6i+T cell inhibitor abatacept (n=1213). Probability and risk for T2DM were estimated with adjustment for relevant confounders.ResultsIn the cohort of 169 242 patients with a mean 4.5 years of follow-up and a mean 641 200 person years of follow-up, the adjusted probability of developing T2DM was significantly lower in the IL-6i (probability, 1%; 95% CI 0.6 to 2.0), T-cell inhibitor (probability, 3%; 95% CI 2.3 to 3.3) and IL-6i+T cell inhibitor (probability, 2%; 95% CI 0.1 to 2.9) groups than in the No bDMARD (probability, 5%; 95% CI 4.6 to 4.9) and TNFi (probability, 4%; 95% CI 3.7 to 4.7) groups. Compared with No bDMARD, the IL-6i and IL-6i+T cell inhibitor groups had 37% (95% CI of HR 0.42 to 0.96) and 34% (95% CI of HR 0.46 to 0.93) significantly lower risk for T2DM, respectively; there was no significant difference in risk in the TNFi (HR 0.99; 95% CI 0.93 to 1.06) and T-cell inhibitor (HR 0.96; 95% CI 0.82 to 1.12) groups.ConclusionsTreatment with IL-6i, with or without T-cell inhibitors, was associated with reduced risk for T2DM compared with TNFi or No bDMARDs; a less pronounced association was observed for the T-cell inhibitor abatacept.

Background:There’s little data of patients with immune diseases (ID) treated with biologic and JAK-inhibitors and COVID19. Current consensus is to keep treatment, however more studies are needed to ascertain the risk in these patients.Objectives:To describe the associated risk factors and outcomes in hospitalized patients with ID treated with biologics and JAK-inhibitors of a tertiary center.Methods:Observational retrospective study of patients with COVID19 from March 1st 2020 to January 31st 2021. Out of all the patients receiving subcutaneous (SC) or intravenous (IV) biologics and oral (PO) JAK-inhibitors, we selected those requiring hospitalization due to pneumonia for analysis. We collected demographic data, comorbidities, seasonal flu vaccination, smoking history and the outcome (discharge/admission in an intensive care unit (ICU)/death). We used a composite index (Charlston’s index) for comorbidities.Results:Of 153 patients, 29 (18.9%) were hospitalized. 18 (62%) were women with a median age of 61 (IQ 52-69). 14 (48.2%) had rheumatoid arthritis, 5 (17%) had axial spondylarthritis and 4 (13.7%) had Chron’s disease. The main IV was Rituximab in 3 (50%), and abatacept, infliximab and vedolizumab had one each. Of the SC, tocilizumab and adalimumab had 5 (22.7%) each, etanecept and golimumab had 3 (13.6%) each and secukinumab, ustekinumab and abatacept had 2 (9%) each. The PO was tofacitinib. There were no outcome differences for each treatment.24 (82.7%) patients had at least 1 comorbidity with significative difference between patients (Table 1). There were 6 (20.6%) deaths, 3 (50%) in the ICU, 2 (33%) did not meet the ICU criteria, and 1 (16%) before ICU admission. None them had the same ID.Table 1.Baseline data.Variables, (%)Total29 (100)Deaths 6 (20.6)Discharged23 (79.3)PWomen (%)18 (62)4 (66.6)14 (61)0.79Age, Median (IQ range)61 (52-69)69.5 (62-78.5)59.9 (51-65.5)0.09Flu vaccine (%)15 (51.7)5 (83.3)10 (43.7)0.08ICU (%)8 (27.5)3 (50)5 (22)0.16TreatmentIV (%)6 (20.1)4 (66.7)2 (8.7)0.001SC (%)22 (75.8)2 (33.3)20 (87)PO (%)1 (3.4)0 (0)1 (4.3)0.6ComorbiditiesCharlston, Mean (standard deviation)2.72 (+/-1.6)5.16 (+/- 1.8)2.08 (+/-1.5)Hypertension/HTA (%)16 (55)5 (83.3)11 (48)0.11Dyslipidemia/DL (%)12 (41.3)4 (66.7)8 (34.8)0.15Obesity (%)10 (34.5)1 (16.7)9 (39.1)0.30Chronic obstructive pulmonary disease/COPD (%)3 (10.3)3(50)0 (0)Heart disease (%)8 (27.5)4 (66.6)4 (17.4)0.01Chronic kidney disease/CKD (%)7 (24.1)4 (66.6)3 (13)0.006Diabetes mellitus /DM (%)7 (24.1)3 (50)4 (17.4)0.001Previous or current smokers (%)9 (31)3 (50)6 (26)0.26Conclusion:The rate of COVID19 hospitalization in our patients was comparable to the general population’s (between 19-24% from 60 years plus) and the risk of in-patient death is also similar, around 24%1. Our study suggests that neither their ID nor their treatment influences their risk of a worse outcome.COPD, DM and previous heart disease were associated with worse outcome; however it seems that the main prognostic factor was the overall impact of comorbidities associated; as measured by the Charlston’s index, being significantly higher in the patients with a fatal outcome.A fatal outcome was more likely in IV biologics, however it could be explained by indication bias probably due to higher comorbidity and disability in these patients rather than an independent prognostic variable.References:[1]Mesas AE et al. Predictors of in-hospital COVID-19 mortality: A comprehensive systematic review and meta-analysis exploring differences by age, sex and health conditions. PLoS One. 2020 Nov 3;15(11)[2]Jovani, V et al.Incidence of severe COVID-19 in a Spanish cohort of 1037 patients with rheumatic diseases treated with biologics and JAK-inhibitors. ARD 2020–218152.Disclosure of Interests:None declared

Background:There are no RA response predictors for our patients. The decision to initiate a first biological depends on multiple factors such as rheumatologist experience, clinical characteristics of the patient and health system. What is clear is that the best strategy is T2T.Objectives:To know the clinical characteristics and persistence of the first biological DMARD in patients receiving bDMARDS TNF inhibitors vs DMARDs aimed at other targets.Methods:A observational cohort of adult RA patients (ACR/EULAR 2010) in a rheumatology department of a third-level university hospital. All patients were treated with a first bDMARD marketed in Spain, from 2010 to December 2020 and prescribed according to product data sheet. Biological drugs were divided into TNF inhibitors drugs (adalimumab, etanercept, infliximab, golimumab, certolizumab) and Other targets (abatacept, rituximab, sarilumab, tocilizumab). Clinical data, duration of treatment and EULAR response were collected from each patient. The data were analyzed with descriptive, bivariate statistics and survival analysis adjusted for age, sex, FR, erosions and duration of the disease.Results:Data were collected from 332 patients (table 1). Patients treated with other target bDMARDs were mostly female, with higher activity, shorter disease duration, and treated without MTX.b Survival graphs showed that regardless of the target chosen as fist bDMARD, EULAR response rates and persistence to the drug were similar.Table 1.VariableTNF inhibitorsn=194Other targetsn = 138Totaln =332pn (%)n (%)n (%)0.02Female142 (73)115 (83)257 (77)0.2FR +163 (82)121 (88)284 (86)0.6ACPA +125 (63)84 (61)209 (63)0.9Erosions177 (89)80 (58)257 (77)0.01Concomitant MTX153 (77)62 (47)215 (65)0.003EULAR response Good103 (77)67 (71)170 (75)0.2 Moderate24 (18)16 (17)40 (17) No7 (5)11 (11)18 (8)Mean ± SDMean ± SDMean ± SDAge (years)55.7 ± 13.357.6 ± 11.956.5 ± 12.70.1Evolution of RA (years)9.6 ± 10.27.5 ± 7.58.7 ± 9.20.04Persistence (months)19.3 ± 20.516.07 ± 15.1117.5 ± 18.50.04DAS28VSG4V basal5.02 ± 1.55.59 ± 1.035.25 ± 1.30.001DAS28VSG4V final2.68 ± 1.12.84 ± 1.42.7 ± 1.250,31Conclusion:Patients receiving Anti-TNF vs bDMARD with other mechanisms of action have clinical differences. However, the response and persistence to the drug are similar, perhaps due to the implementation of the correct T2T strategy.Disclosure of Interests:None declared

Background:WHO declared the COVID-19 outbreak as a pandemic on March 12th, 2020. Assessing the risk of severe course in patients with rheumatic diseases, especially those who receive targeted immunosuppressive treatment, is an urgent problem for rheumatologists.Objectives:determine the relationship between used targeted biologic and synthetic DMARDs (tDMARDs) and the severity of course of COVID-19 infection.Methods:The analysis included the data of patients with chronic arthritis and COVID-19, used tDMARDs. COVID-19 infection was confirm by serology tests or immune system molecules (immunoglobulins/antibodies). The presence of symptoms, the need for hospitalization, and the need for oxygen therapy were considered as indicators of the severity of the infection. We also analyzed the spread of the lung involvement according to CT data, symptoms during the disease (fever, cough, anosmia, diarrhea).Results:Analyses included 78 patients, among them 32 patients has ankylosing spondylitis, 31 patients - rheumatoid arthritis, 12 patients has psoriatic arthritis, 3 patients - juvenile arthritis. The average age of the included patients was 51,8 ± 11,69. Most of patients used TNF inhibitors - 43 (Adalimumab -10, Golimumab -4, Infliximab – 4, Certolizumab pegol -3, Etanercept – 22), JAK inhibitor tofacitinib used 13 patients, 5 patients each was treated with Abatacept and Tocilizumab, 3 patients used Rituximab and 2 patients each used Netakimab and Ustekinumab (Table 1). None of the patients included in the analysis required treatment in the ICU and/or mechanical ventilation. The course of the disease in patients treated with tDMARDs did not seem to be more severe than in 5 patients with arthritis who stopped treatment with tDMARDs before the onset of the pandemic. There was a direct correlation between the severity of the infection and the age of the patients (p=0.007). There were no significant differences in the severity of the infection depending on the drug, including when adjusting for age.Conclusion:COVID-19 does not look extremely dangerous in patients with rheumatic diseases, used target DMARDs. Used of tsDMARDs doesn’t reliably increase the risk of COVID-19 severity. There is reliable correlation between age and COVID-19 severity.Table 1.Cohort characteristicsDrugsMean ageNumber ofpatientsPatientswithsymptomsHospitalized patientsAsymptomaticcourseAdalimumab41,0±11,410921Golimumab51,0±11,034400Infliximab42,7±11,84004Certolizumab41,6±11,73300Etanercept50,7±11,4222062Tofacitinib56,8±10,4131221Abatacept57,4±10,95411Tocilizumab48,8±10.95312Rituximab55,6±10,73310Netakimab44,0±15,82210Ustekinumab48,0±10,52101Disclosure of Interests:None declared

Background:Longer disease duration and greater number of prior DMARDs have been associated with lower treatment efficacy in patients with RA.1 Abatacept is a biologic (b)DMARD for treatment of moderate-to-severe RA and is available in SC formulation, which may offer convenience benefits with efficacy similar to IV administration.2 ASCORE (Abatacept SubCutaneOus in Routine Clinical PracticE; NCT02090556) was a 2-year, observational, prospective, multicentre study of SC abatacept for treatment of RA in routine clinical practice.3Objectives:This post hoc analysis was conducted to determine if retention and efficacy of abatacept were impacted by disease duration and/or treatment line.Methods:Eligible patients, aged ≥18 years, with active moderate-to-severe RA (ACR/EULAR 2010 criteria) who were IV abatacept-naive and initiated SC abatacept 125 mg once weekly, were enrolled into two cohorts: bDMARD-naive patients and those with ≥1 prior bDMARD treatment failure. This post hoc analysis evaluated abatacept retention using Kaplan-Meier estimates, as well as disease activity scores (DAS28 [ESR]), CDAI and SDAI in patients with disease duration of ≤2, 3–5, 6–10 or >10 years, and in patients taking abatacept as first-line or ≥ second-line treatment.Results:Table 1 shows baseline (BL) characteristics. Mean age increased with disease duration; other characteristics were comparable across groups. Retention proportions (95% CIs) at Month 24 were 0.50 (0.4, 0.5), 0.47 (0.4, 0.5), 0.51 (0.5, 0.5) and 0.46 (0.4, 0.5) in the ≤2, 3–5, 6–10 and >10 years’ duration groups, respectively. Proportion of patients (95% CI) with ≤2 years’ duration retaining treatment at Month 24 were 0.51 (0.4, 0.6) among those using abatacept as first-line treatment and 0.44 (0.3, 0.6) among those using abatacept as a ≥ second-line treatment (Figure 1). Proportions (95% CI) at Month 24 were 0.51 (0.5, 0.6), 0.57 (0.5, 0.6) and 0.52 (0.5, 0.6) in first-line patients and 0.43 (0.4, 0.5), 0.48 (0.4, 0.5) and 0.44 (0.4, 0.5) in ≥ second-line patients in the 3–5, 6–10 and >10 years’ duration groups, respectively. Mean (SE) changes from BL in DAS28 (ESR) at Month 24 were –2.12 (0.205), –1.86 (0.151), –2.07 (0.140) and –2.05 (0.115) in the ≤2, 3–5, 6–10 and >10 years’ duration groups, respectively; respective mean (SE) changes in CDAI were –18.74 (1.604), –15.60 (1.099), –18.50 (1.038) and –17.68 (0.850); and respective mean (SE) changes in SDAI were –19.10 (1.873), –15.72 (1.345), –19.54 (1.103) and –17.07 (0.939).Conclusion:In this post hoc analysis of the real-world ASCORE trial, patients with RA receiving abatacept in clinical practice as first-line therapy had better retention versus those receiving it as a ≥ second-line treatment, regardless of disease duration at BL. Retention rates were similar across disease duration subgroups. Improvements in disease activity were seen in all duration subgroups, without consistently greater or lesser improvement seen with longer disease duration.References:[1]Aletaha D, et al. Ann Rheum Dis 2019;78:1609–1615.[2]Genovese MC, et al. Arthritis Rheumatol 2011;63:2854–2864.[3]Alten R, et al. Ann Rheum Dis 2019;78(suppl 2):A1639.Table 1.BL characteristics (n=2872)RA disease duration, years≤2(n=338)3–5(n=655)6–10(n=686)>10(n=1193)Age, years n3386556861193 Mean (SD)55.2 (12.8)55.6 (12.7)56.9 (13.0)59.9 (12.2)Weight, kg n3276296651150 Mean (SD)75.3 (18.1)76.4 (19.0)74.7 (17.4)72.9 (16.0)DAS28 (ESR) n247439441743 Mean (SD)5.2 (1.3)4.9 (1.3)5 (1.2)5.1 (1.3)DAS28 (CRP) n267460467799 Mean (SD)4.7 (1.2)4.6 (1.2)4.7 (1.1)4.7 (1.2)CDAI n269477474805 Mean (SD)26.9 (12.7)25.3 (12.2)26.8 (12.4)26.6 (12.2)SDAI n255448445749 Mean (SD)28.3 (13.3)26.8 (12.9)27.9 (12.6)28.0 (12.7)RF status, n (%) RF+159 (47.0)342 (52.2)345 (50.3)597 (50.0) RF–103 (30.5)152 (23.2)158 (23.0)215 (18.0)Anti-CCP status, n (%) Anti-CCP+165 (48.8)332 (50.7)333 (48.5)516 (43.3) Anti-CCP–89 (26.3)126 (19.2)137 (20.0)175 (14.7)Patients with missing duration of disease are excluded.CCP=cyclic citrullinated peptide.Acknowledgements:Professional medical writing and editorial assistance was provided by Rob Coover, MPH, at Caudex and was funded by Bristol Myers Squibb. This study was funded by Bristol Myers Squibb.Disclosure of Interests:Rieke Alten Speakers bureau: AbbVie, Bristol Myers Squibb, Gilead, Janssen, Lilly, Pfizer, Consultant of: AbbVie, Bristol Myers Squibb, Gilead, Janssen, Lilly, Pfizer, Grant/research support from: AbbVie, Bristol Myers Squibb, Gilead, Janssen, Lilly, Pfizer, Xavier Mariette Consultant of: Bristol Myers Squibb, Galapagos, Gilead, GlaxoSmithKline, Janssen, Pfizer, UCB, Rene-Marc Flipo Speakers bureau: AbbVie, Bristol Myers Squibb, Janssen, Lilly, Medac, Merck Sharp & Dohme, Novartis, Pfizer, Roche-Chugai, Grant/research support from: Amgen, Janssen, Novartis, Pfizer, Roberto Caporali Speakers bureau: AbbVie, Amgen, Bristol Myers Squibb, Celltrion, Fresenius Kabi, Galapagos, Gilead, Lilly, Merck Sharp & Dohme, Pfizer, Roche, Samsung Bioepis, Sanofi, UCB, Consultant of: Galapagos, Gilead, Janssen, Lilly, Merck Sharp & Dohme, Maya H Buch Speakers bureau: AbbVie, Consultant of: AbbVie, Eli Lilly, Gilead, Merck Serono, Pfizer, Roche, Sanofi, Grant/research support from: Gilead, Pfizer, Roche, UCB, Yusuf Patel: None declared, Raimón Sanmartí Speakers bureau: AbbVie, Bristol Myers Squibb, Gebro, Janssen, Lilly, Merck Sharp & Dohme, Pfizer, Roche, Sanofi, Consultant of: AbbVie, Bristol Myers Squibb, Gebro, Lilly, Merck Sharp & Dohme, Pfizer, Roche, Sanofi, Grant/research support from: Bristol Myers Squibb, Merck Sharp & Dohme, Pfizer, Sara Marsal Speakers bureau: Bristol Myers Squibb, Celgene, Pfizer, Roche, Sanofi, UCB, Consultant of: AbbVie, Bristol Myers Squibb, Celgene, Galapagos, Merck Sharp & Dohme, Pfizer, Roche, Sanofi, UCB, Grant/research support from: AbbVie, Bristol Myers Squibb, Celgene, Janssen, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Sanofi, UCB, M.T. Nurmohamed Speakers bureau: AbbVie, Bristol Myers Squibb, Eli Lilly, Roche, Sanofi, Consultant of: AbbVie, Celgene, Celltrion, Eli Lilly, Janssen, Grant/research support from: AbbVie, Bristol Myers Squibb, Celgene, Eli Lilly, Janssen, Merck Sharp & Dohme, Mundipharma, Novartis, Pfizer, Roche, Sanofi, Hedley Griffiths Consultant of: AbbVie, Gilead, Janssen, Novartis, Peter Peichl: None declared, Bettina Bannert: None declared, Adrian Forster: None declared, Melanie Chartier Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Yedid Elbez Consultant of: Bristol Myers Squibb, Christiane Rauch Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Vadim Khaychuk Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Karissa Lozenski Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb

Background:Abatacept, a selective inhibitor of T cell co-stimulation, is often used as a second-line biologic disease-modifying anti-rheumatic drug (bDMARD) after the failure of tumour necrosis factor inhibitor (TNFi) in Rheumatoid Arthritis (RA). However, in comparison to TNFi very few survival analyses of abatacept have been reported.1,2Objectives:To investigate predictors of abatacept discontinuation due to either inefficacy or adverse events in RA patients over 5-years.Methods:A retrospective observational analysis was conducted on a tertiary hospital dataset of RA (according to 2010 ACR/EULAR criteria) patients who started abatacept (either intravenous or subcutaneous). Time to abatacept discontinuation over 5-years was estimated using Kaplan-Meier survival analyses. A multivariate cox-regression model to predict abatacept discontinuation was chosen by elastic net regularisation.Results:A total of 112 patients with RA [81% female, mean age 58.1 (SD 13.5) years] commenced abatacept therapy during the study period. 88 (78.6%) patients received intravenous abatacept, 14 (15.9%) of whom switched to subcutaneous injection, and 24 (21.4%) were initially treated with subcutaneous abatacept, 2 (8.3%) of whom switched to intravenous. More than half of the patients (65/112) were treated with at least one concomitant conventional synthetic DMARD (csDMARD). Methotrexate was the most commonly used (n = 37) csDMARD, followed by hydroxychloroquine (n = 23), sulfasalazine (n= 15), and leflunomide (n = 7). 42 (37.5%) patients were treated with glucocorticoids (either oral, intra-articular, or intramuscular injection) during the time they were treated with abatacept. Abatacept was most commonly used as 4th (n = 29) and 3rd line (n = 24) bDMARD but 19 patients received abatacept as their first line bDMARD. 75 (67%) patients were rheumatoid factor (RF) positive and 73 (65.2%) were anti-citrullinated protein antibody (ACPA) positive. Anti-nuclear antibody (ANA) was positive in 32 patients. Abatacept was discontinued in 54 patients (48.2%); 19 (35.2%) due to an adverse event and 35 (64.8%) due to loss of efficacy. Overall, the median time to discontinuation of abatacept was 3.8 years.Multivariate cox regression (variables chosen by the elastic net and adjusted by whether or not abatacept was used as first-line therapy) showed that ACPA positivity was associated with a reduced risk of abatacept discontinuation with a hazard ratio (HR) of 0.40 (95% CI 0.18 to 0.85, p=0.02, N. of events 16/47) compared to ACPA negative patients (N. of events 15/23), but only if ANA was negative. In contrast, ACPA positivity did not reveal any retention benefit over ACPA negative patients, if they were ANA positive.ACPA positive patients without positive ANA increased the time-to-discontinuation of abatacept predominantly after 3-months (unadjusted log-rank p=0.02), compared to ACPA, and ANA negative patients (Figure 1). Adding csDMARDs with abatacept, reduced the risk of discontinuation of abatacept by 59% (95% CI 24% to 77%, p = 0.004, N. of events 26/65) compared to monotherapy (N. of events 28/47).Conclusion:Our data suggests patients who are ACPA positive and ANA negative are more likely to remain on abatacept therapy. Concomitant csDMARD use also acts as a positive predictor of abatacept treatment retention.References:[1]Cagnotto G, et al. Arthritis Res Ther. 2020;22(1):15.[2]Alten R, et al. Clin Rheumatol. 2019;38(5):1413-1424.Figure 1.Kaplan-Meier survival curve of retention of abatacept, stratified by Anti-citrullinated protein antibody (ACPA) and antinuclear antibody (ANA).+ACPA/-ANA = ACPA positive and ANA negative, +ACPA/+ANA = ACPA positive and ANA positive, -ACPA/-ANA = ACPA negative and ANA negative, -ACPA/+ANA = ACPA negative and ANA positive, HR = Hazard ratio.Acknowledgements:I have no acknowledgements to declare.Disclosure of Interests:None declared

Background:The ORIGAMI study is a multicenter, observational study to evaluate the effectiveness, safety, and patient-reported outcomes of abatacept (ABA) in Japanese patients with csDMARD-resistant, Simplified Disease Activity Index (SDAI)-moderate, biologic-naïve rheumatoid arthritis (RA). ABA has shown better effectiveness/efficacy in RA patients with anti-cyclic citrullinated peptide antibody (ACPA) positive (1) and high ACPA titer (2) compared to ACPA negative and low ACPA titer, respectively. However, more accurate predictors of effectiveness in clinical practice are needed than ACPA status.Objectives:This post-hoc analysis is aimed to determine the association between ACPA and ABA effectiveness (disease activity and physical function) or retention rate and to investigate other factors associated with the effectiveness of ABA in patients enrolled in the ORIGAMI study.Methods:Of the 279 patients in the effectiveness analysis set of the ORIGAMI study, 270 patients with baseline ACPA measurement were analyzed. The patients were divided into the ACPA-positive group (ACPA +ve, ≥4.5 U/mL at baseline) and the ACPA-negative group (ACPA –ve, Results:The numbers of ACPA +ve and –ve patients were 226 and 44, respectively. ACPA values (mean ± SD, U/mL) were 280.3 ± 376.8 and 0.9 ± 0.7, and rheumatoid factor (RF) values were 174.8 ± 302.6 and 20.9 ± 61.7 in the ACPA +ve and –ve groups, respectively. Mean (95% confidence interval) changes in SDAI at week 52 were −11.3 (−12.4 to −10.3) and −8.0 (−10.5 to −5.5), and those in J-HAQ were −0.27 (−0.34 to −0.20) and −0.16 (−0.34 to 0.01) in the ACPA +ve and –ve groups, respectively. In the Kaplan–Meier analysis, the retention rates of ABA at week 52 in the ACPA +ve and –ve groups were 72.1% and 58.7%, (discontinuation for any reason), and 91.6% and 75.7% (discontinuation because of lack of effectiveness), respectively. In a multiple regression analysis, the duration of disease (< 1 year) was associated with the change in SDAI at week 52. With respect to SDAI changes, the estimated difference of ACPA +ve and disease duration (< 1 year), ACPA +ve and disease duration (≥1 year), and ACPA –ve and disease duration (< 1 year), versus ACPA −ve and disease duration (≥ 1 year), were −4.26 (p = 0.022), −0.82 (p = 0.618), and −0.93 (p = 0.716), respectively (Fig. 1). The estimated difference of ACPA +ve and RF +ve, ACPA +ve and RF –ve, and ACPA –ve and RF +ve, versus ACPA –ve and RF –ve, were −2.48 (p = 0.060), −2.77 (p = 0.107), and −5.48 (p = 0.087), respectively.Conclusion:A higher retention rate as well as better effectiveness of ABA on disease activity and physical function in ACPA +ve group versus ACPA –ve group were shown in the simple subgroup analysis. ABA effectiveness on the SDAI change was significantly better in patients with disease duration References:[1]Harrold LR et al. J Rheumatol 2018;45(1):32–39.[2]Sokolove J et al. Ann Rheum Dis 2016;75(4):709–714.Disclosure of Interests:Kenta Misaki Speakers bureau: Eisai Co., Ltd., AbbVie GK, Eli Lilly Japan K.K., Ono Pharmaceutical Co., Ltd., Grant/research support from: Ono Pharmaceutical Co., Ltd., Eiichi Tanaka Speakers bureau: AbbVie GK, Asahi Kasei Pharma Corporation, Astellas Pharma Inc, Ayumi Pharmaceutical Corporation, Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., Eli Lilly Japan K.K., GlaxoSmithKline K.K., Kyowa Pharma Chemical Co., Ltd., Janssen Pharmaceutical K.K., Mochida Pharmaceutical Co., Ltd., Pfizer, Takeda Pharmaceutical Co., Ltd, and Teijin Pharma Ltd., Eisuke Inoue Speakers bureau: Pfizer Japan, Bristol-Myers Squibb K.K., Katsuki Tsuritani Employee of: Bristol-Myers Squibb K.K., Shigeru Matsumoto Employee of: Ono Pharmaceutical Co., Ltd., Hisashi Yamanaka Consultant of: Bristol-Myers Squibb K.K., masayoshi harigai Speakers bureau: AbbVie GK, Ayumi Pharmaceutical Corporation, Bristol-Myers Squibb K.K., Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., Eli Lilly Japan K.K., Pfizer Japan Inc., and Takeda Pharmaceutical Co., Ltd., Consultant of: AbbVie GK, Bristol-Myers Squibb K.K., Chugai Pharmaceutical Co., Ltd., Eli Lilly Japan K.K., and Gilead Sciences Inc., Grant/research support from: AbbVie GK, and Asahi Kasei Corp., Astellas Pharma Inc., Ayumi Pharmaceutical Corporation, Bristol-Myers Squibb K.K., Chugai Pharmaceutical Co., Ltd. Daiichi-Sankyo, Inc., Eisai Co., Ltd., Mitsubishi Tanabe Pharma Corporation., Nippon Kayaku Co., Ltd., Taisho Pharmaceutical Co., Ltd., and Takeda Pharmaceutical Co., Ltd.

Background:Up to 50% of patients with RA discontinue DMARD treatment within 18 months.1 However, up to 20% of patients who fail multiple treatments may have a good treatment response to another therapy.1 Predictive biomarkers, such as RF and anti-citrullinated protein antibodies (ACPAs), may be useful to stratify patients with RA to the most appropriate treatment.1 ASCORE (Abatacept SubCutaneOus in Routine Clinical PracticE; NCT02090556) was a 2-year, observational, prospective, multicentre study of SC abatacept for the treatment of RA in routine clinical practice.2Objectives:To determine if RF/ACPA serostatus and treatment line impact abatacept retention in patients with RA in a post hoc analysis of ASCORE.Methods:Eligible patients, aged ≥18 years, with active moderate-to-severe RA (ACR/EULAR 2010 criteria) who were IV abatacept-naive and initiated SC abatacept 125 mg once weekly, were enrolled into two cohorts: biologic (b)DMARD-naive patients and those with ≥1 prior bDMARD treatment failure. This post hoc analysis assessed abatacept retention rate at 2 years in a subset of patients with RF/ACPA serostatus data (n=1748) from the ASCORE study (N=2892; as observed). Baseline (BL) serostatus groups examined by treatment line were: RF/ACPA double positive (+/+) RA, RF/ACPA single positive (RF+/ACPA– or RF–/ACPA+) RA (data not shown) and RF/ACPA double negative (–/–) RA. Last observation carried forward (LOCF) analyses were used to assess change from BL and measures of disease remission (DAS28 [CRP] Results:BL demographic and disease characteristics were similar across serostatus groups and treatment lines (Table 1). Mean age was 57.1 and 57.8 years for +/+ RA and –/– RA, respectively. Mean DAS28 (CRP) was 4.7 and 4.8 for +/+ RA and –/– RA, respectively. In patients with +/+ RA, abatacept retention was greater when given as first-line treatment (57% vs 48% when given as ≥ second-line) (Figure 1). Retention was similar in patients with –/– RA regardless of treatment line. After 2 years, mean (SE) change from BL (LOCF) in DAS28 (CRP) was –1.41 (0.06) and –0.97 (0.09) for patients with +/+ and –/– RA, respectively. For patients with +/+ RA, mean (SE) change from BL in DAS28 (CRP) was –1.62 (0.08) for those in whom abatacept was first-line and –1.19 (0.08) for those in whom abatacept was ≥ second-line. For patients with –/– RA, mean (SE) change from BL in DAS28 (CRP) was –1.03 (0.13) for those in whom abatacept was first-line and –0.93 (0.12) for those in whom abatacept was ≥ second-line. Remission rates (LOCF) were significantly (pTable 1.BL demographics and disease characteristics by RF/ACPA status+/+ RA(n=1079)–/– RA(n=343)First-line (n=511)≥ second-line (n=568)First-line(n=140)≥ second-line(n=203)Age57.1 (13.4)57.1 (12.2)59.5 (14.7)56.6 (13.2)DAS28 (CRP)4.7 (1.2)4.7 (1.2)4.8 (1.1)4.8 (1.2)CDAI26.6 (12.5)26.6 (12.4)27.7 (12.5)28.6 (13.8)SDAI28.1 (13.1)28.1 (12.9)29.1 (12.9)30.2 (14.7)Data are mean (SD). Patients with missing data for BL RF/ACPA status are excluded.ACPA=anti-citrullinated protein antibody; BL=baseline.Conclusion:In this real-world analysis, patients with +/+ RA treated with first-line abatacept had higher retention than patients receiving abatacept as a ≥ second-line therapy. Remission rates on abatacept were higher in patients with +/+ RA versus –/– RA. These results support early treatment with abatacept and highlight the importance of further evaluating precision medicine approaches in RA.References:[1]Smolen JS, et al. Ann Rheum Dis 2020;79:685–699.[2]Alten R, et al. Ann Rheum Dis 2019;78(suppl 2):A1639.Acknowledgements:Professional medical writing and editorial assistance was provided by Lindsay Craik at Caudex and was funded by Bristol Myers Squibb. This study was funded by Bristol Myers Squibb.Disclosure of Interests:Rieke Alten Speakers bureau: AbbVie, Bristol Myers Squibb, Gilead, Janssen, Lilly, Pfizer, Consultant of: AbbVie, Bristol Myers Squibb, Gilead, Janssen, Lilly, Pfizer, Grant/research support from: AbbVie, Bristol Myers Squibb, Gilead, Janssen, Lilly, Pfizer, Xavier Mariette Consultant of: Bristol Myers Squibb, Galapagos, Gilead, GlaxoSmithKline, Janssen, Pfizer, UCB, Rene-Marc Flipo Speakers bureau: AbbVie, Bristol Myers Squibb, Janssen, Lilly, Medac, Merck Sharp & Dohme, Novartis, Pfizer, Roche-Chugai, Grant/research support from: Amgen, Janssen, Novartis, Pfizer, Roberto Caporali Speakers bureau: AbbVie, Amgen, Bristol Myers Squibb, Celltrion, Fresenius Kabi, Galapagos, Gilead, Lilly, Merck Sharp & Dohme, Pfizer, Roche, Samsung Bioepis, Sanofi, UCB, Consultant of: Galapagos, Gilead, Janssen, Lilly, Merck Sharp & Dohme, Maya H Buch Speakers bureau: AbbVie, Consultant of: AbbVie, Eli Lilly, Gilead, Merck Serono, Pfizer, Roche, Sanofi, Grant/research support from: Gilead, Pfizer, Roche, UCB, Yusuf Patel: None declared, Raimón Sanmartí Speakers bureau: AbbVie, Bristol Myers Squibb, Gebro, Janssen, Lilly, Merck Sharp & Dohme, Pfizer, Roche, Sanofi, Consultant of: AbbVie, Bristol Myers Squibb, Gebro, Lilly, Merck Sharp & Dohme, Pfizer, Roche, Sanofi, Grant/research support from: Bristol Myers Squibb, Merck Sharp & Dohme, Pfizer, Sara Marsal Speakers bureau: Bristol Myers Squibb, Celgene, Pfizer, Roche, Sanofi, UCB, Consultant of: AbbVie, Bristol Myers Squibb, Celgene, Galapagos, Merck Sharp & Dohme, Pfizer, Roche, Sanofi, UCB, Grant/research support from: AbbVie, Bristol Myers Squibb, Celgene, Janssen, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Sanofi, UCB, M.T. Nurmohamed Speakers bureau: AbbVie, Bristol Myers Squibb, Eli Lilly, Roche, Sanofi, Consultant of: AbbVie, Celgene, Celltrion, Eli Lilly, Janssen, Grant/research support from: AbbVie, Bristol Myers Squibb, Celgene, Eli Lilly, Janssen, Merck Sharp & Dohme, Mundipharma, Novartis, Pfizer, Roche, Sanofi, Hedley Griffiths Consultant of: AbbVie, Gilead, Janssen, Novartis, Peter Peichl: None declared, Bettina Bannert: None declared, Adrian Forster: None declared, Melanie Chartier Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Sean Connolly Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Yedid Elbez Consultant of: Bristol Myers Squibb, Christiane Rauch Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Vadim Khaychuk Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Karissa Lozenski Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb

Background:At a time when vaccines are being prioritized for individuals most at risk, there is currently no clear evidence that risk of SARS-CoV-2 infection is higher for patients with than without inflammatory arthritides (IA). Biologic use was not associated with worse COVID-19 outcomes for yet but the case of rituximab (RTX) remains an issue, given its immunological long term effect, the role of humoral response against SARS-CoV-2 and its indirect effect on T-cell response. A potential association between rituximab and worse COVID-19 outcomes was raised by case reports and retrospective, declarative studies (with few data on the total number of patients exposed).Objectives:To address differently the issue of the risk of COVID-19 related to RTX and limit biases, we examined the occurrence of severe COVID-19 in all patients receiving intravenous biologic agents at day-hospitals during the pandemic in France.Methods:From 1st September 2019 to 1st January 2021, we analyzed patients with IA prospectively treated with intravenous biologic agents (RTX, abatacept, infliximab or tocilizumab) in 7 clinical centers in France. We obtained the list of patients receiving intravenous biologic agents in each center from the pharmacist of the hospitals. Therefore, all consecutive patients receiving 1 of the 4 drugs at the time of the study were included in each center. Patients with no follow-up after September 2020 were systematically contacted by phone. The occurrence of a severe COVID -19 (i.e. resulting in death, hospitalization or increase in length of hospitalization related to COVID-19) was the primary outcome criteria.Results:In total, 1116 patients receiving intravenous biologic agents were included: 449 with infliximab, 392 RTX, 170 tocilizumab and 105 abatacept. From 1st September 2019, the median follow-up time was 15 months (interquartile range 14-16). In total, 10 cases of severe COVID-19 occurred, 9 treated with RTX and 1 with infliximab (supplementary Table 1). Four deaths occurred in our cohort during follow-up but none was related to COVID-19 (1 patient treated by tocilizumab, 1 by RTX and 2 by infliximab). In univariate analysis, the proportion of severe COVID-19 was significantly higher for patients receiving RTX than other biologic agents (9/392 vs 1/724, p=0.0003, OR [95%CI] 17.0 [2.1-134.6]). To take into account potential confounders, we performed multivariate analysis accounting for baseline parameters that differed between RTX and other biologic groups. RTX remained significantly associated with risk of severe COVID-19 (p=0.019) (Table 1).Patient characteristicsRituximab (n= 392)Other bDMARDs (n= 724)Univariate analysis, p-valueMultivariate analysis, p-valueMedian age (years), — [IQR]64 [56-71]57.3 [47.0-67.0]< 0.00010.51Female — n (%)285 (72.7)426 (58.8)< 0.00010.58IA diagnosis< 0.00010.12Median follow-up from 1st September to last news14 [13-15]15 [14-16]< 0.00010.86Confirmed severe COVID-19 cases —n (%)9 (2.3)1 (0.1)0.00030.019Comorbidities** (history of) — n (%) Cardiovascular disease60 (15.4)167 (23.1)0.00250.77 Chronic lung disease,92 (23.5)84 (11.6)0.00010.88Median BMI (kg/m2) — [IQR]25.8 [23.2-29.4]27.3 [23.4-31.2]0.0150.80Treatments — n (%) Methotrexate179 (45.8)322 (44.5)0.71 Leflunomide41 (10.5)39 (5.4)0.00230.43 Hydroxychloroquine35 (8.9)24 (3.3)0.00010.15 Glucocorticoids127 (41.8)100 (19.4)< 0.00010.36 Median dose (mg/day) — [IQR]1 [0-5]0 [0-0]< 0.0001No significant difference in terms of baseline gammaglobulins (p=0.46) or number of previous RTX infusions (p=0.57) was observed among patients receiving RTX with or without a severe COVID-19.Conclusion:The present results highly indicate increased risk of severe COVID-19 with RTX. Among patients with inflammatory arthritides, those receiving RTX should be prioritized for vaccination against SARS-CoV-2, sufficiently long before infusion/reinfusion and the immunization checked, or an alternative targeted therapy proposed.Acknowledgements:We thank Dr. Karine Demesmay and all the pharmacists who helped us for this study.Disclosure of Interests:Renaud FELTEN Speakers bureau: Abbvie, Biogen, BMS, Lilly, Novartis, Pfizer, Pierre-Marie Duret: None declared, Elodie BAUER: None declared, Marc Ardizzone: None declared, H Julien Djossou: None declared, Jean-Hugues Salmon: None declared, Cassandre Fabre: None declared, Julia Walther: None declared, Isabelle CHARY VALCKENAERE: None declared, marion geoffroy: None declared, Laurent Messer: None declared, Francis Berenbaum: None declared, Martin SOUBRIER: None declared, Jérémie SELLAM Speakers bureau: MSD, Pfizer, Abbvie, Roche, BMS, Lilly, Janssen, Novartis, Galapagos, Sandoz, Fresenius Kabi, Grant/research support from: Roche, MSD, Pfizer, Jacques-Eric Gottenberg: None declared

Background:Modes of action of DMARDs (disease-modifying antirheumatic drugs) in rheumatoid arthritis (RA) are not completely understood at the level of the synovium. Studying treatment-induced modifications in RA synovial tissue can provide unique insights into the pathways modulated downstream of different DMARDs.Objectives:Our goal was to assess histological and transcriptomic effects of Abatacept (ABA) on RA synovium, and to compare them with previously published data obtained by our group using the same study design on other DMARDs: Tocilizumab (TCZ), Rituximab (RTX), Methotrexate (MTX) and Adalimumab (ADA).Methods:Synovial tissue was obtained using ultrasound-guided biopsy from affected joints before (W0) and 16 weeks (W16) after treatment with subcutaneous Abatacept 125mg per week on a MTX background. Paraffin-sections were stained for CD3, CD20 and CD68 and scored by a pathologist for T cell, B cell and macrophage infiltration. Transcriptional profiling was performed using GeneChip Human Genome U133 Plus 2.0 arrays (Affymetrix), and analyzed on Genespring GX (Agilent). Pathway analyses were performed on Genespring GX, Metascape (https://metascape.org/) and EnrichR (https://maayanlab.cloud/Enrichr/). Protein-Protein Interaction (PPI) networks were generated on STRING (https://string-db.org/).Results:14 RA patients were included (female: 9, ACPA/RF positive: 8, erosive disease: 12, median disease duration in years (± SD): 11.7 (± 8.1), median DAS28CRP (± SD): 4.78 (± 1.11)). Median DAS28CRP significantly decreased between W0 and W16, as did US GS score. Evaluation of histological slides (n=11 pairs of samples) showed no significant effect of Abatacept on T cell, B cell or macrophage infiltration. Gene expression analysis (n=10 pairs of samples) identified 304 transcripts differentially expressed (129 downregulated, 175 upregulated) between W0 and W16 (FC≥1.5 and pIL2RA, CD28, IL7, IL7R), strongly overlapping with data from previous studies on TCZ (n= 12 pairs), RTX (n=12 pairs), MTX (n=8 pairs) and ADA (n=8 pairs). Thus, each treatment shares 31 to 48% of its downregulated genes with the others, with genes downregulated by at least three involved in key RA-associated pathways such as leukocyte activation, NF-kappa B signaling, TNF signaling and JAK-STAT signaling. Given their seemingly overlapping effects, data were pooled across these studies, markedly improving power thanks to their paired-design. This revealed that genes downregulated by DMARDs (n=573, Benjamini-Hochberg corrected p-valueT cell and myeloid leukocyte activation pathways. Interestingly, DMARDs seem to have a coordinate effect on the two pathways (correlation of mean Log2FC: r=0.8558, p2FCW16-W0) in good responders to therapy (n=17) as compared to moderate (n=20) and to non-responders (n=13) (pConclusion:We provide evidence that the effects of five DMARDs on RA synovium culminate in the same pathways (namely, T cell and myeloid leukocyte activation). This confirms previous studies suggesting the existence of common mediators downstream of DMARDs, independent of their primary targets, and suggests attractive new therapeutic targets.Acknowledgements:This work was funded in part by unrestricted grants from Cap48 (RTBF) and Bristol-Myers Squibb. Clément Triaille is funded by the Fonds National de la Recherche Scientifique (FNRS, Communauté française de Belgique) and Fondation Saint-Luc (Cliniques Universitaires Saint-Luc).Disclosure of Interests:Clément Triaille: None declared, Tilman Gaelle: None declared, Tatiana Sokolova: None declared, Laurent Meric de Bellefon: None declared, Christine Galant: None declared, Patrick Durez Grant/research support from: unrestricted research grant from Bristol-Myers Squibb, Bernard Lauwerys Employee of: currently employed at UCB Biopharma, Nisha Limaye: None declared

Background:In the phase 3 double-blind SELECT-CHOICE study of patients (pts) with prior inadequate response (IR) or intolerance to biologic disease-modifying antirheumatic drugs (bDMARDs), upadacitinib (UPA) showed superiority to abatacept (ABA) in change from baseline in 28-joint Disease Activity Score using C-reactive protein (DAS28[CRP]) and in the proportion of pts achieving DAS28(CRP) Objectives:To describe clinical responses in pts receiving UPA or ABA by number and mechanism of action of prior bDMARDs.Methods:612 pts were randomized to once-daily UPA 15 mg or monthly intravenous ABA (100 kg, 1000 mg). All pts continued background therapy with stable conventional synthetic DMARDs. From Week 12, pts who did not achieve ≥20% improvement in both tender and swollen joint counts vs baseline at 2 consecutive visits had background medication(s) adjusted or added. In this post hoc analysis, pts were grouped by the number and/or type of bDMARD received prior to enrollment: 1) lack of efficacy (LoE) to ≥1 tumor necrosis factor (TNF) inhibitor; 2) LoE to ≥1 interleukin-6 (IL-6) inhibitor; 3) intolerance to prior bDMARDs; 4) number of prior bDMARDs (1, 2, or ≥3). Mean change from baseline in DAS28(CRP) and DAS28(CRP) Results:Most pts had LoE to ≥1 TNF inhibitor (536, 87.6%); 96 (15.7%) had LoE to an IL-6 inhibitor; 79 (12.9%) had intolerance to prior bDMARDs; 408 (66.7%), 134 (21.9%), and 64 (10.5%) had received 1, 2, or ≥3 prior bDMARDs, respectively. Mean change from baseline in DAS28(CRP) was generally greater with UPA vs ABA across the different pt subgroups at Weeks 12/24 (Figure 1). Across endpoints, regardless of prior bDMARD therapy (except in those who failed ≥3 prior bDMARDs), UPA and ABA demonstrated similar responses at Week 12 compared with those observed for the overall treatment groups, even with more stringent criteria such as ACR70 and Clinical Disease Activity Index (CDAI) ≤2.8 (Table 1. below) Responses at Week 24 followed a similar trend to those at Week 12 for DAS28(CRP) Table 1.Efficacy endpoints by prior bDMARD subgroup (Week 12 [top] and Week 24 [bottom])aACR20ACR50ACR70DAS28(CRP)≤3.2DAS28(CRP) CDAI ≤10CDAI ≤2.8HAQ-DIMCIDbLoE to ≥1 TNF inhibitorUPA 15 mg n=26375.377.944.959.722.838.849.061.230.446.840.758.69.122.875.574.3ABAn=27364.572.933.748.413.224.927.546.512.529.733.749.82.212.565.266.3LoE to ≥1 IL-6 inhibitorUPA 15 mg n=4870.885.437.566.720.829.245.866.725.041.741.758.36.316.778.378.3ABAn=4877.179.241.756.322.927.125.043.814.629.227.152.12.110.475.075.0Intolerance to prior bDMARDsUPA 15 mgn=4783.076.653.257.417.027.753.257.431.929.844.744.78.514.980.073.3ABAn=3262.571.928.150.00.031.321.956.36.331.321.956.33.19.461.367.71 priorbDMARDUPA 15 mgn=20677.281.151.963.121.838.852.466.032.547.641.761.29.220.979.676.6ABAn=20267.377.735.153.515.833.729.251.512.435.636.155.93.016.366.771.72 priorbDMARDsUPA 15 mgn=6478.176.634.456.323.439.151.662.526.650.045.354.74.723.473.870.5ABAn=7064.364.328.642.94.311.427.141.411.424.328.644.31.48.655.755.7≥3 prior bDMARDsUPA 15 mg n=2955.265.524.144.817.224.127.641.420.727.627.648.310.317.258.672.4ABAn=3565.771.440.040.020.017.128.637.120.020.037.140.02.98.677.174.3aMissing information was imputed using NRI. bHAQ-DI MCID=reduction from baseline of ≥0.22ACR20/50/70, 20/50/70% improvement in ACR criteria; HAQ-DI, Health Assessment Questionnaire-Disability IndexConclusion:Although sample sizes were small for some subgroups, treatment with UPA led to greater clinical responses vs ABA at Week 12, including in pts with LoE to TNF or IL-6 inhibitors, and those with IR or intolerance to 1, 2, or ≥3 prior bDMARDs.Acknowledgements:AbbVie funded this study; contributed to its design; participated in data collection, analysis, and interpretation of the data; and participated in the writing, review, and approval of the abstract. No honoraria or payments were made for authorship. Medical writing support was provided by Grant Kirkpatrick, MSc of 2 the Nth (Cheshire, UK), and was funded by AbbVie.Disclosure of Interests:Andrea Rubbert-Roth Consultant of: AbbVie, Amgen, Bristol-Myers Squibb, Chugai, Eli Lilly, Gilead, Janssen, Novartis, Roche, and Sanofi, Ricardo Xavier Consultant of: AbbVie, Amgen, Bristol-Myers Squibb, Eli Lilly, Janssen, Novartis, Pfizer, and UCB, Boulos Haraoui Consultant of: AbbVie, Amgen, Eli Lilly, Gilead, MSD, Pfizer, Sandoz, and UCB, Herbert S.B. Baraf Consultant of: Gilead, Janssen, and UCB, Grant/research support from: AbbVie, Eli Lilly, Genentech, Gilead, and Janssen, Maureen Rischmueller Consultant of: AbbVie, Bristol-Myers Squibb, CSL Behring, Eli Lilly, Gilead, Janssen, Pfizer, Sanofi, and UCB, Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, Eli Lilly, Janssen, Novartis, Pfizer, Sanofi, and UCB, Naomi Martin Shareholder of: May own stock or options in AbbVie, Employee of: AbbVie, Yanna Song Shareholder of: May own stock or options in AbbVie, Employee of: AbbVie, Jessica Suboticki Shareholder of: May own stock or options in AbbVie, Employee of: AbbVie, John Cush Consultant of: AbbVie, Amgen, Bristol-Myers Squibb, and Novartis.

Background:Interstitial lung disease (ILD) is a severe extra-articular manifestation of rheumatoid arthritis (RA). However, the effect of RA treatment on the course of ILD is not yet known.Objectives:To assess the effect of RA treatment on the course of lung physiology of RA-focusing on biologic DMARDs treatment.Methods:The Korean Rheumatoid Arthritis ILd (KORAIL) cohort is the prospective observational cohort and aims to investigate the natural course of RAILD. Based on either 1987 or 2020 ACR criteria, patients diagnosed with RA and ILD based on CT scan were recruited from six tertiary medical hospitals in Korea since January 2015. RA disease activity was assessed using disease activity (DAS)28-ESR and CRP, annually. Pulmonary function tests (PFT), including FVC and DLCO were conducted annually. In the current study, we analyzed patients who completed a 2-years follow-up or had died during those terms till October 2020. They classified patients into three groups: patients treated with abatacept ≥24 weeks ever (Group 1), those with other bDAMRDs ≥24 weeks ever (Group 2), and those without any bDMARDs or with bDMARDs Results:Of a total of 125 patients who completed 2-year follow-up, 21 patients were classified as Group 1, 26 for Group 2, and 78 for Group 3. The mean age or the number of patients with ≥ 65-year-old was comparable between groups(Table 1). The mean duration since RA diagnosis was shorter in Group 3, but that since ILD diagnosis was comparable. DAS28-ESR score was comparable between Group 1 and 2 at enrollment, so was in 1-year-follow-up (p=0.75) and 2-year-follow-up (p=1.00). FVC and % of the predicted value in FVC, FEV1, and DLco were also comparable among the three groups at enrollment. The numbers of patients with ≥10-point decline in % of FVC predicted was 2 (10.0%) for Group 1, 1 (3.8%) for Group 2, 3 (3.9%) for Group3 during the first 1-year follow-up, and 3 (15.8%), 3 (11.5%), 10 (14.1%) during the last 1-year follow up. The percent of FVC predicted was 81.6 ± 17.5 %, 87.4 ± 17.9 %, 85.2 ± 17.7 % for Group 1,2 and 3, respectively, at 1-year-follow-up, and 79.5 ± 18.8 %, 89.0 ± 16.8 %, 83.5 ± 17.3 % at 2-year-follow-up. (Figure 1A). The percent of DLco predicted was 75.5 ± 23.4 %, 66.7 ± 18.1 %, 67.5 ± 16.7 % for Group 1,2 and 3, respectively, at 1-year-follow-up, and 74.0 ± 23.7 %, 69.1 ± 18.9 %, 67.0 ± 18.5 % at 1-year-follow-up (Figure 1B).Conclusion:Treatment of bDMARDs did not exacerbate FVC than without bDMARDs treatment and mitigated the decline of DLCO compared to without bDMARDs treatment during 2-year-follow-up.Table 1.Clinical characteristics at enrollment (V1)TotalGroup 1.Group 2.Group 3.PN125212678Age at enrollment65.9±8.266.0±8.863.9±8.066.6±8.10.3465, n (%)72 (57.6)13 (61.9)11 (42.3)48 (61.5)0.21Female, n (%)89 (71.2)16 (76.2)17 (65.4)56 (71.8)0.71RA duration, years8.0±8.49.6±6.69.2±9.07.2±8.60.05ILD duration, years3.0±3.33.8±3.73.8±3.52.5±3.10.10BMI, kg/m224.1±3.123.8±3.724.8±2.923.9±3.00.39Ever-smoker1855180.57RF positive, n (%)111 (88.8)19 (90.5)22 (84.6)70 (89.7)0.72Anti-CCP positive, n (%)119 (95.2)20 (95.2)25 (96.2)74 (94.9)1.00Arthritis activityDAS28-ESR4.0 ± 1.44.1 ± 1.14.3 ± 1.83.8 ± 1.40.60*DAS28-CRP3.1 ± 1.43.2 ± 1.23.4 ± 1.63.0 ± 1.40.76*HAQ-DI0.70 ± 0.760.64 ± 0.490.82 ± 0.820.67 ± 0.800.28*Pulmonary function testFVC, ml2522.5 ± 765.42406.2 ± 772.62617.3 ± 965.22522.2 ± 692.30.65FVC, % of pred.84.6 ± 16.980.9 ± 17.786.12 ± 17.8285.08 ± 16.50.53FEV1, % of pred.92.4 ± 21.492.0 ± 24.890.6 ± 22.193.0 ± 20.40.88DLco, % of pred.71.5 ± 19.772.3 ± 26.769.1 ± 16.472.0 ± 18.70.80Figure 1.Acknowledgements:This research was supported by Bristol Myers Squibb Inc.Disclosure of Interests:Sung Hae Chang: None declared, Ji Sung Lee: None declared, Jeong Seok Lee: None declared, Chan Ho Park: None declared, Min Uk Kim: None declared, You-Jung Ha: None declared, Eun Ha Kang: None declared, Yeon Ah Lee: None declared, Yongbeom Park: None declared, Jung-Yoon Choe: None declared, Eun Young Lee Grant/research support from: Bristol Myers Squibb Inc.

Background:Rheumatoid arthritis (RA) is the most common autoimmune disease. Older patients treated with biologic DMARDs (bDMARDs) are at a significantly greater risk of adverse effects (AEs) [1]. However, the rate of drug discontinuation because of adverse effects caused by bDMARDs has not differed in elderly compared to younger patients in different registries.Objectives:Determine if drug discontinuation of bDMARDs differs by age in patients with rheumatoid arthritis in the Mexican Adverse Events Registry (BIOBADAMEX).Methods:BIOBADAMEX is a Mexican ongoing cohort of patients using bDMARDs since 2016. In this analysis we included all patients with diagnosis of RA with at least two assessments. Survival on bDMARDs was estimated using Kaplan-Meier analysis. Predictors of discontinuation, including age older than median age in the sample were investigated by Cox regression analyses.Results:Among 743 patients in the registry, 497 had RA diagnosis, from which, 214 had at least two assessments. At baseline, patients had a median (IQR) age of 53.4 (45-61) years old, median disease duration of 10.7 (6-17) months and median DAS28 of 4.7 (3-6). Conventional DMARDS were used by 185 (87%) patients and 94 (44%) patients used corticosteroids. Comorbidities were present in 194 (91%). The most common bDMARDs received at baseline were abatacept 59 (27%), tocilizumab 45(21%), adalimumab 31 (15%) and certolizumab 30 (14%). At the time of analysis, the median bDMARDs treatment duration was 21.0(13-34) months, 128 (59%) had discontinued treatment, 66 for inefficacy, 32 for adverse events and 30 for others. Fig 1 shows discontinuation rate curves in patients younger and older than median age. Cox proportional-hazards demonstrated no significant differences regarding age older than median age (HR 1.1, 95% CI 0.8-1.4, p=0.7), female sex (HR 1.2, 95% CI 0.7-1.9, p=0.44), use of corticosteroids (HR 1.2, 95% CI 0.9-1.6, p=0.20), comorbidities (HR 0.9, 95% 0.6-1.5, p=0.78), DAS28 (HR 0.9, 95% 0.9-1.1, p=0.93) or other factors.Figure 1.Discontinuation rate curves in patients younger and older than median age (< 53.4 and >=53.4 years old)Conclusion:This analysis did not show a role of age on discontinuation of bDMARDs in Mexican RA patients. Further longitudinal analyses will be performed including more patients to assess retention rate of bDMARDs and identify predictive variables of discontinuation in Mexican population.References:[1]Akter R, et al. Can Geriatr J. 2020 May 1;23(2):184-189.[2]Ikari Y, et al. Medicine (Baltimore). 2020 Dec 24;99(52):e23861.Disclosure of Interests:None declared

Background:Chronic kidney disease (CKD) is defined as a permanent (minimum three month) reduction in glomerular filtration rate. [1] 10-30% of rheumatoid arthritis (RA) patients have CKD, compared to 5% of the general population.[1] There are several causes of CKD associated with RA including persistent inflammation, cardiovascular risk factors, frequent use of non-steroidal anti-inflammatory drugs and amyloidosis.[1] CKD in RA patients is associated with increased mortality.[2]The use of biologic and targeted synthetic DMARDs for treating RA has increased significantly in recent years. Studies have shown these therapies might reduce the risk of developing CKD in RA. [3] However, conversely, biologics have been linked to the development of glomerulonephritis.[4]Surprisingly few studies have explored the use of biologics in patients with pre-existing renal disease and whether they contribute to renal impairment themselves.Objectives:Our objectives were to explore the renal safety profile of biologic and targeted synthetic DMARDs in a real-world cohort of RA patients with and without pre-existing CKD.Methods:A retrospective observational study was completed using the Biologic Therapy Database at Cannock Chase Hospital. Inclusion criteria were a diagnosis of RA and current treatment with a biologic or targeted synthetic DMARD.Demographic data, renal function at biologic initiation and any deterioration of renal function were among the recorded information for each patient. Patients with insufficient information available via electronic patient records were excluded.Results:998 RA patients on biologics were identified, of whom 213 were excluded. Of the 785 remaining patients, a 3:1 female to male ratio was noted with a mean age of 62. 40% of patients were on an anti-TNF, 22% rituximab, 15% abatacept, 15% JAK inhibitors and 9% anti-IL6 respectively. At biologic initiation 92% of the patients had a GFR of >60 ml/min per 1.73m2, 4.8% had a GFR of 30-60 (CKD stage 3a-3b), Overall, 13 patients had significant pre-existing CKD (eGFR Of those patients without prior CKD at the point of biologic initiation (GFR >45), only 15 patients (2%) developed new renal impairment whilst on biologic treatment. 10 patients’ renal function dropped by one stage and five patients by two stages. Crucially, 12 of the 15 patients were aged ≥75yrs and 10 patients had at least one other associated risk factor (e.g. diabetes). Only one patient in the cohort developed renal impairment as a direct result of a biologic - minimal-change disease secondary to etanercept.Conclusion:Our findings indicate that biologic treatments have a good renal safety profile – even with pre-existing CKD. RA patients most at risk of developing CKD whilst on biologics are likely to have other risk factors such as diabetes or hypertension. As previously stated, there is a very rare association of anti-TNF biologics causing glomerulonephritis.References:[1]Couderc M, et al. Prevalence of Renal Impairment in Patients with Rheumatoid Arthritis: Results from a Cross-Sectional Multicenter Study. Arthritis Care Res. 2016 May 1;68(5):638–44.[2]Chiu HY, et al. Increased risk of chronic kidney disease in rheumatoid arthritis associated with cardiovascular complications - A national population-based cohort study. PLoS One. 2015 Sep 25;10(9).[3]Sumida K, et al. Treatment of rheumatoid arthritis with biologic agents lowers the risk of incident chronic kidney disease. Kidney Int. 2018 May 1;93(5):1207–16.[4]Piga M, et al. Biologics-induced autoimmune renal disorders in chronic inflammatory rheumatic diseases: Systematic literature review and analysis of a monocentric cohort. Vol. 13, Autoimmunity Reviews. Elsevier; 2014. p. 873–9.Disclosure of Interests:None declared

Background:The Janus kinase inhibitors (JAKi) have been increasingly used for the treatment of rheumatoid arthritis (RA) in Sweden, with baricitinib representing ~80% of prescriptions. Evidence regarding the comparative effectiveness of JAKis versus biologics (bDMARDs), and in particular non- tumour-necrosis-factor inhibitor (TNFi) bDMARDs, in real-life is limited.Objectives:To compare RA patients treated with bDMARDs and JAKi in Sweden, in terms of: (1) patient characteristics at treatment start; (2) proportions of patients remaining on therapy, and response rates, at 12 months.Methods:RA patients starting treatment in 2017 and 2018 with either a TNFi, rituximab, abatacept, interleukin 6 inhibitors (IL6i) or a JAKi as different lines of treatment were identified in the Swedish Rheumatology Quality Register. One patient could contribute with more than one treatment episode.Treatment response at 12 months was measured as EULAR good response, HAQ improvement >0.2 units, DAS28 and CDAI remission, and as 0 tender and swollen joint counts (28JC). Patients were classified as non-responders if they stopped treatment before evaluation due to safety or inefficacy. Responses for patients who stopped treatment due to pregnancy or death and patients on treatment but with missing response were imputed using multiple imputation.Proportions of responders and differences in proportions between treatment groups, adjusted using inverse probability of treatment weighting, were estimated using linear regression with robust standard errors.Results:JAKi were often used after bDMARDs, and less frequently prescribed in combination with methotrexate. Measured comorbidities were less frequent among JAKi initiators than among non-TNFi biologic initiators, but RA activity was similar (Table).Table 1.Patient characteristics at treatment initiationCharacteristicMedian (IQR) or N (%)AbataceptIL6iRituximabTNFiJAKiTreatment Starts6945346923497905Age63 (53-71)59 (48-70)65 (54-73)59 (47-68)60 (51-70)Female543 (78)441 (83)519 (75)2739 (78)759 (84)RA duration (years)13 (5-21)10 (5-18)12 (6-22)9 (3-17)13 (7-22)Rheum. factor535 (79)385 (73)588 (87)2405 (70)686 (77)DAS284.8 (3.9-5.6)4.9 (4.0-5.7)4.7 (3.8-5.5)4.4 (3.4-5.3)4.7 (3.9-5.7)HAQ1.3 (0.8-1.6)1.3 (0.8-1.8)1.3 (0.8-1.8)1.0 (0.5-1.4)1.3 (0.8-1.8)Tender joints5 (2-9)6 (3-10)5 (2-9)4 (2-8)6 (2-10)Swollen joints4 (2-6)4 (2-7)4 (2-7)3 (1-6)4 (2-7)ts/bDMARD line3 (2-4)3 (2-4)2 (1-4)1 (1-2)4 (2-6)At least one prev. TNFi539 (78)442 (83)457 (66)1448 (41)770 (85)At least one prev. non-TNFi271 (39)220 (41)243 (35)441 (13)584 (65)Methotrexate co-treatment264 (50)172 (40)286 (53)1708 (62)296 (40)Glucocorticoids co-treatment247 (47)186 (43)275 (51)1126 (41)389 (53)Cancer*90 (2.8)64 (2.3)363 (7.7)410 (1.8)20 (2.2)Cardio-vascular dis.*245 (7.5)123 (4.4)322 (6.8)749 (3.4)41 (4.4)Chronic respiratory dis.*303 (9.3)140 (5.0)473 (10.0)721 (3.2)50 (5.4)Diabetes*324 (9.9)216 (7.7)456 (9.7)1479 (6.7)69 (7.5)* any diagnosis within 5 years before start Adjusted differences in proportion with each response outcomeIn a crude comparison, 65% (61%-68%) of JAKi, 62% (59%-66%) of abatacept, 58% (53%-62%) of IL6i, 80% (77%-83%) of rituximab and 68% (67%-70%) of TNFi initiators remained on treatment at 12 months after start. Also, JAKi showed lower overall responder proportions than TNFi, rituximab and IL6i.After adjustment for demographic and socio-economic factors, RA disease activity, previous use of ts/bDMARDs, co-medication with glucocorticoids and methotrexate and comorbidities at baseline, no significant differences in responder proportions between JAKi and bDMARDs remained (Figure). Furthermore, the adjusted proportions of patients on treatment were higher for JAKi and rituximab than for the other bDMARDs.Conclusion:This preliminary analysis of patients treated in clinical practice found no statistically significant difference in effectiveness between JAKi and bDMARDs.Disclosure of Interests:Andrei Barbulescu: None declared, Johan Askling Grant/research support from: Abbvie, Astra-Zeneca, BMS, Eli Lilly, MSD, Pfizer, Roche, Samsung Bioepis, Sanofi, and UCB. These entities have entered into agreements with Karolinska Institutet with JA as principal investigator, mainly in the context of safety monitoring of biologics via the ARTIS national safety monitoring system, Katerina Chatzidionysiou Speakers bureau: Eli Lilly, Abbvie and Pfizer, Consultant of: Eli Lilly, Abbvie and Pfizer, Helena Forsblad-d’Elia: None declared, Alf Kastbom Employee of: Sanofi, Ulf Lindström: None declared, Carl Turesson Speakers bureau: Abbvie, Bristol-Myers Squibb, Medac, Pfizer, Roche, Consultant of: Roche, Grant/research support from: Bristol-Myers Squibb, Thomas Frisell: None declared

Background:T-cells play a pivotal role in the pathogenesis of rheumatoid arthritis (RA) and in its cardiovascular (CV) comorbidities, acting at microvascular level [1]. Since small artery remodeling is the earliest form of target organ damage in hypertension, the evaluation of microvascular alterations might provide clinically useful information. The evaluation of retinal arterioles is a non-invasive technique to identify a precocious microvascular damage, which is related to an increase of the wall-to-lumen ratio (WLR) [2]. CD3+CD31+CXCR4+ T-cells may be involved in damaged endothelium repair and are increased in patients with morphological microvascular alterations [3]. In addition to its effect on disease activity, abatacept (ABA), a co-stimulator blocker which is approved for the treatment of RA, may have specific CV protective action, modulating the numbers of certain subtypes of lymphocytes [4].Objectives:To non-invasively investigate morphological characteristics of retinal arterioles and to evaluate CD3+CD31+CXCR4+T-cells in a cohort of RA patients treated with ABA.Methods:Eleven RA patients [median (25th-75thpercentile) age=58 (50-65) years, baseline C-reactive protein (CRP)-DAS28=4.4 (3.8-4.6), body mass index (BMI)=23.4 (21.6-25.6) kg/m2, rheumatoid factor (RF) positive:45%, anti-citrullinated peptide autoantibodies (ACPA) positive:73%] without known CV risk factors (arterial hypertension, diabetes, hypercholesterolemia, previous CV events, smoking) were evaluated by adaptive optics, a validated technique quantifying microvascular damage [5], before and every 6 months of therapy with ABA (T0, T6 and T12). Phenotypic analysis of peripheral blood T lymphocytes was made by flow-cytometry in 5 patients of the cohort at T0 and T6.Results:A progressive significant reduction of the WLR of retinal arterioles was observed [T0=0.28 (0.25-0.30), T6=0.27 (0.24-0.31), T12=0.23 (0.23-0.26); p T0 vs T6=0.4; p T6 vs T12=0.01; p T0 vs T12=0.01] (Figure 1), without significant variations in the other parameters [internal diameter: T0=94.4 (84.1-104.0), T6=94.8 (84.6-107.7), T12=99.2 (89.1-109.1) µm; external diameter: T0=125.8 (111.1-131.0), T6=122.4 (109.1-134.5), T12=125.6 (113.9-134.4) µm; wall thickness: T0=13.2 (12.2-14.4), T6=13.4 (11.7-14.4), T12=12.5 (11.6-13.0) µm; wall cross-sectional area: T0=4581.0 (3788.7-5263.7), T6=4563.3 (3788.5-5295.2), T12=4099.7 (3899.0-5145.7) µm2)]. In 5 patients evaluated also for T-cell immunophenotyping a negative correlation was observed between CD3+CD31+CXCR4+ T-cell number and the retinal wall thickness at baseline (R=0.871;p=0.05). After ABA therapy a trend for reduction of CD3+CD31+CXCR4+T-cells [19.0 (13.8-38.3) vs 12.4 (5.2-18.0) % of CD3+], was observed as well as of significant reduction of retinal wall cross-sectional area [5123.3 (4385.0-5470.3) vs 4852.3 (4118.3-5228.0) µm2;p=0.04].Conclusion:In a cohort of RA patients without known CV risk factors, a reduction in retinal microvascular alterations arterioles was demonstrated after treatment for 12 months with ABA. CD3+CD31+CXCR4+T-cell number was inversely related to the possible presence of subclinical CV involvement. These results may suggest the possibility of microvascular abnormalities regression induced by the immune system modulation.References:[1]Dessein PH, J Rheumatol 2005.[2]Rizzoni D, Am J Hypertens. 2018.[3]Hur J, Circulation 2007.[4]Kallikourdis M, Nat Commun 2017.[5]De Ciuceis C, J Hypertens 2018.Acknowledgements:Bristol-Myers-Squibb Italy provided an unrestricted research grant for the study conduct.Figure 1.Disclosure of Interests:None declared

Background:Several large randomised controlled trials (RCTs) in primary Sjögren’s syndrome (pSS) failed to demonstrate drug efficacy.1-4 Many of these trials used ESSDAI as primary endpoint, showing large but similar response rates in active treatment and placebo groups.1,3,4 Given the heterogeneous nature of pSS, there is need for a composite endpoint including multiple clinically relevant parameters.Objectives:To develop and validate the Composite of Relevant Endpoints in Sjögren’s Syndrome (CRESS).Methods:A multidisciplinary team of pSS experts selected clinically relevant items and measurements to include in the CRESS. Definition of response of CRESS items was based on clinical relevance, previously defined minimal clinically important improvement (MCII) and data of the single-centre ASAP-III (abatacept) trial.1 CRESS was validated in three independent RCTs: TRACTISS (rituximab) trial2, multi-centre abatacept trial3 and ETAP (tocilizumab) trial4. CRESS response rates were assessed at the primary endpoint visit of all four trials.Results:Five complementary items were selected to form CRESS: systemic disease activity, patient-reported symptoms, tear gland, salivary gland and serological item. Definition of response per item is presented in Table 1. Total CRESS response was defined as response on ≥3 of 5 items. Since not all trials have ocular staining score or salivary gland ultrasonography (SGUS) available, the concise CRESS (cCRESS) was developed simultaneously, leaving Schirmer’s test and unstimulated whole saliva flow for the tear and salivary gland items, respectively. In the ASAP-III trial, CRESS response rates were 24/40 (60%) for abatacept vs. 7/39 (18%) for placebo at week 24 (pTable 1.CRESS items and definition of responseItemsMeasurementsDefinition of responseSystemic disease activityClinESSDAIScorePatient-reported symptomsESSPRIDecrease of ≥1 point or ≥15%Tear gland*Schirmer/OSS**-If abnormal Schirmer (≤5 mm) at baseline: increase of ≥5 mm in Schirmer-Or if abnormal OSS (≥3 points) at baseline: decrease ≥2 points in OSS-Or if both Schirmer/OSS normal scores at baseline: no change to abnormal in bothSalivary gland*UWS/SGUSIncrease of ≥25% in UWS (or if score is 0 at baseline, any increase)Or decrease of ≥25% in total Hocevar score (SGUS)SerologicalRF/IgGDecrease of ≥25% in RFOr decrease of ≥10% in IgGCRESS responderResponder on ≥3 of 5 itemsOcular Staining Score (OSS), Unstimulated whole salivary flow (UWS), Salivary gland ultrasonography (SGUS), Rheumatoid factor (RF), Immunoglobuline G (IgG)*Concise CRESS (cCRESS): CRESS without OSS and SGUS, leaving Schirmer and UWS for tear and salivary gland items, respectively**Mean of both eyesIn the external validation trials, cCRESS response rates for TRACTISS were: 33/67 (49%) rituximab vs. 20/66 (30%) placebo at week 48 (p=0.026). CRESS response rates (without SGUS) for the multi-centre abatacept trial were: 41/92 (45%) abatacept vs. 30/95 (32%) placebo at week 24 (p=0.067). cCRESS response rates (without rheumatoid factor) for ETAP were: 10/55 (18%) tocilizumab vs. 13/55 (24%) placebo at week 24 (p=0.482) (Figure 1A-D). Compared to ESSDAI MCII of ≥3 points decrease, CRESS was able to approximately halve placebo response rates in RCTs with high baseline ESSDAI scores (>5) (Figures 1E-H).Conclusion:CRESS shows lower placebo response rates compared to ESSDAI MCII, which is crucial for demonstrating treatment efficacy. With the CRESS, higher response rates in abatacept and rituximab treated patients compared to placebo were found in RCTs which previously showed negative primary endpoint results. CRESS confirmed that no differences were found for almost all outcome measures between tocilizumab and placebo,4 with low response rates. The CRESS is a well-balanced, feasible, composite endpoint for use in clinical trials in pSS patients.References:[1]Van Nimwegen 2020;9913(19):1–11[2]Bowman 2017;69(7):1440–50[3]Baer (doi:218599)[4]Felten (doi:21846)Acknowledgements:The authors would like to acknowledge all contributors of the included trials.Disclosure of Interests:Suzanne Arends: None declared, Liseth de Wolff: None declared, Jolien F. van Nimwegen Speakers bureau: Bristol Myers Squibb, Consultant of: Bristol Myers Squibb, Gwenny M. Verstappen: None declared, Jelle Vehof: None declared, Michele Bombardieri Consultant of: MedImmune, GlaxoSmithKline, Grant/research support from: MedImmune, Simon J. Bowman Consultant of: AstraZenecea/MedImmune, Bristol Myers Squibb, Celgene, Eli Lilly, Glenmark, GlaxoSmithKline, MTPharma, Novartis, Ono, Pfizer, Takeda, UCB, XTLBio, Elena Pontarini: None declared, Alan Baer Consultant of: Bristol Myers Squibb, Sanofi, VielaBio, Novartis, Marleen Nys Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Jacques-Eric Gottenberg Grant/research support from: Bristol Myers Squibb, Pfizer, Renaud FELTEN: None declared, Neelanjana Ray Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Arjan Vissink: None declared, Frans G.M. Kroese Speakers bureau: Bristol Myers Squibb, Roche and Janssen-Cilag, Consultant of: Bristol Myers Squibb, Grant/research support from: Unrestricted grants from Bristol Myers Squibb, Hendrika Bootsma Speakers bureau: Bristol Myers Squibb and Novartis, Consultant of: Bristol Myers Squibb, Roche, Novartis, Medimmune, Union Chimique Belge, Grant/research support from: Unrestricted grants from Bristol Myers Squibb and Roche

Background:Biological disease modifying anti-rheumatic drugs (bDMARDs) and Janus Kinase inhibitors (JAKi) are both recommended post conventional synthetic disease modifying anti-rheumatic drug (csDMARD) therapy failure in active rheumatoid arthritis (RA), but the data on long-term durability are limited.Objectives:The objective of this study is to analyze a database of patients at the Western University, Rheumatology Center who initiated a bDMARD or JAKi and compare the proportion and characteristics of patients associated with retention of a drug class.Methods:This was a single-center study of 215 adult RA patients (82.76 % females, age 59.8 ± 12.0 years, disease duration 15.5 ± 10.0 years; table 1) failing multiple csDMARDs prior to initiating either bDMARDs (TNF inhibitors, abatacept, rituximab, tocilizumab) or JAKi, between June 2014 (when tofacitinib was approved in Canada) and April 2020. All patients enrolled had failed traditional DMARDs, including methotrexate, hydroxychloroquine, sulfasalazine and/or leflunomide. Durability and predictors of discontinuation were analyzed by Kaplan-Meier and Cox regression analyses for all treatment trials, and for patients receiving bDMARDs/JAKi as a first line after csDMARDs failure.Results:In 215 patients, there were 320 treatment events (148 bDMARDs, 172 JAKi) and 142 discontinuations (53.5% bDMARDs, 46.5% JAKi). Figure 1 represents the Kaplan-Meier survival curve for time to therapy discontinuation in 215 patients receiving bDMARDs vs JAKi. The Cox proportional hazards model was significant with better retention for JAKi, with a hazard ratio (HR) for treatment discontinuation of JAKi compared with bDMARDs of 0.676 (95% CI 0.47-0.97, p=0.034), adjusted for gender, age, disease duration, and line of therapy (Table 1). Moreover, the analysis revealed better retention for both groups as first line advanced therapy compared to later lines of therapy; 57.6% of JAKi and 31.1% of bDMARDs were used as first line advanced therapy. HR for treatment discontinuation for first line vs later lines of therapy was 0.593 (95% CI 0.40-0.88, p=0.01), adjusted for drug class, gender, age, and disease duration (Table 1). The most common reasons for discontinuations were inefficacy (60%), side effects (22%), or other reasons (18%). Inefficacy (58% vs 62%, p=0.8) and side-effects (16% vs 27%, p=0.4) were equally common for bDMARDs and JAKi. Sex, age at treatment onset, and RA duration did not predict discontinuation by Cox regression analyses, and after sub-grouping into bDMARDs and JAKi.Conclusion:EULAR guidelines have placed bDMARDs equal to JAKi as post csDMARD failure therapy in active RA. However, this study demonstrates that JAKi has a greater durability than biologics regardless of gender, age, disease duration, and line of therapy. Therefore, JAKi may be considered as a preferable method of treatment post csDMARD failure in active RA.Figure 1.Kaplan-Meier survival curves for (A) time to discontinuation of therapy in all RA patients receiving bDMARDs versus JAKi; P-value represents Cox regression adjusted for gender, age, disease duration, and line of therapy (B) time to discontinuation of therapy in patients using bDMARDs/JAKi as first line of advanced therapy; P-value represents Cox regression adjusted for drug class, gender, age, and disease durationTable 1.Patient demographics and hazard ratios for discontinuation of bDMARDs versus JAKi by Cox regression modelCharacteristicJAKi (N=172)bDMARD (N=148)MeanAge (years)60.958.559.8Sex (% F)77.888.582.8Disease duration (years)15.315.815.5Line of advanced therapy (% first line)57.631.145.3Drug used (%)Tofacitinib: 93.5Rituximab: 26.4Etanercept: 19.6Adalimumab: 17.6Predictors of Drug DiscontinuationHR (95% CIs)P valuesCrude ModelJAKi vs bDMARDs0.60 (0.43, 0.84)0.003Adjusted modelJAKi vs bDMARDs0.68 (0.47, 0.97)0.034Male vs female0.77 (0.46, 1.31)0.342Age1.01 (0.99, 1.03)0.123RA duration0.99 (0.97, 1.01)0.500Treatment line 1 vs >10.59 (0.40, 0.88)0.010Disclosure of Interests:Karla Machlab: None declared, Samir M. Iskandar: None declared, Tatiana Nevskaya: None declared, Louise Vanderhoek: None declared, Jillian Bylsma: None declared, Sara Hewitt: None declared, Janet Pope Speakers bureau: AbbVie, Amgen, BMS, BI, Gilead, Galapagos, Janssen, Lilly, Medexus, Merck, Novartis, Pfizer, Sanofi, Sandoz, Consultant of: AbbVie, Amgen, BMS, BI, Celltrion, Gilead, Galapagos, Janssen, Lilly, Medexus, Merck, Novartis, Pfizer, Roche, Samsung, Sanofi, Sandoz, Teva, UCB, Grant/research support from: AbbVie, BMS, Merck, Pfizer, Roche, Seattle Genetics

Background:The COVID-19 pandemic requires measures to reduce patient exposure to the risk of contamination, in particular by limiting hospital admissions and promoting lockdown. In order to respond to these healthcare measures, patients were offered to replace intravenous infusions (IV) of abatacept (ABT) and tocilizumab (TCZ) to subcutaneous injections (SC).Objectives:To assess the outcome of patients who switched from IV ABT or TCZ to SC during the COVID-19 pandemic.Methods:A survey was conducted in December 2020 in partnership with the national AFP-RIC patient association to assess the outcome and satisfaction of patients who switched from ABT or TCZ IV to SC during the first wave of COVID-19 pandemic.We also analysed the outcome of patients who switched from IV ABT or TCZ to SC in the rheumatology department of Cochin Hospital during the lockdown in April/may 2020. Articular activity parameters (swollen joint count, pain joint count, visual analogic pain scale, CRP, DAS-28 activity score) were assessed at medical visits before and 6 months after switching from IV to SC.The data collected from the AFP-RIC patient association and the rheumatology department of Cochin Hospital were then aggregated and analyzed by Chi-square and Wilcoxon tests.Results:81 patients responded to the survey carried out by AFP-RIC patient association, including 29 treated with IV ABT (n=15, 52%) or TCZ (n=14, 48%). 17/29 (59%) were offered to switch from IV to SC, 14/17 patients (82%) accepted and 7 patients were still receiving ABT or TCZ SC injections in December 2020. In the rheumatology department of Cochin hospital, 71 patients were scheduled in April/May 2020 to receive IV ABT or TCZ, and 27 (38%) switched to SC. After 6 months, 19 patients (70%) had maintained SC injections, were satisfied with this injection route of administration and their articular activity parameters were unchanged (Table 1).Table 1.Course of Disease parameters evaluated in the 19 patients who maintained abatacept or tocilizumab SC injections in the Rheumatology department of Cochin HospitalParameter, mean(SD)Inclusion visitSwitch to SC(n=19)6 month visit (n=19)P-valueDAS282.3 (1.2)2.3 (0.7)0.62Tender joint count2.5 (3.5)1.3 (1.7)0.49Swollen joint count1.3 (2.5)0.9 (0.6)0.35Patient Global Health (cm)3.2 (1.9)2.6 (1.8)0.60CRP (mg/L)3.2 (4.1)5.2 (4.9)0.56CRP: C-Reactive Protein, SD: Standard DeviationThe combined analysis of these two populations included 41 patients (33 rheumatoid arthritis, RA, 7 juvenile idiopathic arthritis, JIA and 1 polymyalgia rheumatica) who switched to SC ABT or TCZ. 26/41 (63.5%) patients maintained SC injections and IV was re-established in 15/41 (36.5%). Reasons for returning to IV were poor tolerance of SC injections (n=6, 40%), worsening symptoms (n=11, 73%), patient preference to see a rheumatologist in hospital (n=10, 67%) and the high number of SC injections (n=2, 13%). The proportion of patients returning to IV was higher in RA patients compared to patients with JIA (42% vs. 14%, p = 0.08). Age and disease duration were not significantly different between patients who maintained SC injections and those who returned to IV (respectively p=0.97 and p=0.63).Conclusion:Our study suggests that switching from IV ABT or TCZ to SC is an acceptable procedure during the COVID-19 pandemic, especially for patients with JIA.Acknowledgements:Association AFP-RIC (Angélique Hochedé, Cyrielle Beller, Sandrine Rollot) and the members of the association for their help in the conduction of the surveyDisclosure of Interests:None declared.

Background:Systemic juvenile idiopathic arthritis (sJIA) is one of the most perplexing diseases of childhood, with a wide range of presentation features and severity. Advances in treatment have improved the outcome, such as the use of modulators of proinflammatory cytokines and their receptors, but in a considerable number of children, especially in polyarticular or sJIA, refractoriness tends to be progressive. As of late, extreme cases have required Autologous Stem Cell Transplantation (ASCT) as a last resort.Objectives:To describe an extremely refractory clinical evolution in a sAIJ patient, the first one to be submitted to an ASCT for an autoinflammatory condition in Brasília, Brazil’s capital.Methods:Case ReportThe patient was classified according to the Pediatric International League of Associations for Rheumatology for sJIA.I.T.S.M, female, 15-years-old, was diagnosed with sJIA at 6 with the onset of polyarthritis, daily fever for 6 weeks, rash and enlargement of liver and spleen. In the initial investigation infectious and neoplastic causes were ruled out.The use of prednisone and methotrexate lead to a preliminary effective clinical control, however after an year, there was clinical deterioration and etanercept was associated, leading to a short term improvement. At that time, in addition to anti-tumour necrosis factor medications, no other biological drugs were available in Brazil.Despite some brief periods of clinical improvement, after different regimes, the patient manifested recurrent flares. Since the diagnosis she has already been treated with:[1]Methotrexate (2011 to 2014*, 2016 to 2020). *In 2015, it was replaced by Leflunomide (up to May 2016, discontinued due to intolerance);[2]Etanercept (2012);[3]Cyclosporine (August to December 2012);[4]Adalimumab (2013);[5]Tocilizumab (May 2014 to January 2015);[6]Canaquinumab (March 2015 to April 2016);[7]Mycophenolate Mofetil (February 2016, discontinued in May 2017 due to start of Cyclophosphamide);[8]Rituximab (May 2016 to April 2017);[9]Cyclophosphamide at a dose of 2 grams /m2 as well as Filgrastim for mobilization and collection of stem cells (May 2017, in a attempt of ASCT), but the parents were unable to reach a mutual agreement to consent to the continuation of this therapy;[10]Cyclophosphamide (500mg /m2) in a mensal scheme application for nine consecutive months since June 2017, once was observed a clinical improvement after the intensive immunosuppression previous to ASCT attempt;[11]Several courses of methylprednisolone and human immunoglobulin since the initial diagnosis;[12]Abatacept (November 2019 to October 2020);[13]ASCT was suggested again in 2020, this time with the consent of all family members.Results:An intensive immunosuppression [Cyclophosphamide and anti-thymocyte globulin (ATG)] followed by ASCT (October 2020) resulted in apparent sustained remission. The patient’s evolution since the transplant has been optimistic. She is currently on a low dose prednisone prescription. To ensure a less profound depletion of T cells, a better control of systemic disease and antimicrobial and antiviral prophylaxis after transplantation, slow tapering of corticosteroids were performed.Conclusion:The goal of hematopoietic stem cell transplantation in patients with autoimmune disease is to reprogram the immune system with the eradication of autoreactive cells, renew the population of regulatory T cells and restore the diversity of T cell receptor function.ASCT has been used in some refractory children with sJIA as well as hematologic malignancy and some progressive autoimmune diseases. However it is associated with significant morbidity and mortality, due to prolonged and severe depression of T cell immunity.References:[1]D.M.C. Brinkman et al. Arthritis Care & Research (2007)[2]Voltarelli Júlio C. et al. Rev. Bras. Hematol. Hemoter. (2010)[3]Angelo De Cata et al. Clin Exp Med. (2016)[4]Joost F. Swart et al. Nature Reviews Rheumatology (2017)Acknowledgements:We kindly thank the Hematology service of Hospital da Criança de Brasília, where the patient was subjected to the autologous stem-cell transplantation.Disclosure of Interests:None declared

Background:polymyalgia rheumatica (PMR) is a chronic inflammatory disorder affecting elderly people. Glucocorticoids (GC) are the mainstay of therapy for PMR. Despite this treatment, the disease may relapse or GC dosage cannot be tapered. Methotrexate (MTX) may be helpful in these cases. Blockade of IL-6 has an effective steroid-sparing effect in patients with giant cell arteritis (GCA) and may improve the clinical symptoms of patients with PMR. The pathophysiology of PMR still remains uncertain but there are evidences for a participation of Th1 and Th17 lymphocytes. Recently, blockade of the costimulatory pathway by abatacept (ABA) gave favorable results in GCA.Objectives:to report our experience (efficacy and safety) of ABA in the treatment of patients with isolated PMR who required longstanding GC and who failed to respond to MTX and/or IL-6 receptor blocking agents.Methods:a call for observations of all cases of patient with PMR who received at least one dose (SC or IV) of ABA was sent to the members of the French specialist network “Club Rhumatismes & Inflammation” (CRI: www.cri-net.com)(rheumatologist and internal medicine). Patients must satisfy the EULAR/ACR criteria for PMR and have isolated PMR without associated GCA.Results:4 cases were declared during a 12 months period: 2 men and 2 women; age (median [range]): 60.7 [50-68] years; disease duration 30 [7-48] months; duration of GC treatment before starting ABA: 60 [10-72] months. They all required prednisolone with a daily dosage of 14.5 mg [10-20]. Before ABA administration, they all received MTX while 2 patients were treated by IL-6R inhibitor (tocilizumab 6 months and sarilumab 3 months, respectively) without improvement. ABA was given as a monthly infusion (10 mg/kg) in one case and subcutaneously (every week) in 3 cases. ABA treatment duration ranged from 3 to 18 months. Two patients responded to the treatment with a progressive decline of DAS-PMR and GC dosage tapering during a 12 month follow-up, while there was no improvement for the 2 others (Table 1). CRP levels also decreased for one responder. The safety was excellent for all. ABA was still maintained in one responder. Among the non-responders, one patient was switched to tocilizumab and the second still received high GC dosage.Conclusion:ABA may be effective in certain PMR patients who were unable to taper GC, with a good safety profile. A randomized controlled trial is required in order to determine its place in the treatment of PMR and to select the appropriate patients who could potentially benefit from this biological agent.References:[1]Langford CA et al. Vasculitis Clinical Research Consortium. A Randomized, Double-Blind Trial of Abatacept (CTLA-4Ig) for the Treatment of Giant Cell Arteritis. Arthritis Rheumatol. 2017; 69: 837-845Table 1.changes in DAS-PMR and CRP levels in 4 patients with PMR while receiving abatacept (M: months; CRP in mg/L).CasesDAS- PMR M0DAS- PMR M3DAS-PMR M6DAS -PMR M12CRP M0CRP M3CRP M6CRP M121202121NA58.68.4NA231.130.5NANA2125NANA310.78.3551337.222.722224182217.2121.23.33.53Disclosure of Interests:None declared

Background:Biomarkers are commonly used as prognostic tools in rheumatoid arthritis (RA) and have additional potential to guide treatment decisions. Previous clinical trials of abatacept (ABA) such as the Early AMPLE trial (eAMPLE) and real-world data suggest differential treatment effects of ABA based on the presence of biomarkers and disease stage.1-4Objectives:To supplement evidence of enhanced efficacy of ABA among patients with enriched autoantibody biomarkers and early disease stage by applying key inclusion criteria from the eAMPLE trial retrospectively to historic ABA RCTs.Methods:Individual patient data (IPD) from four early-RA ABA trials (AGREE [NCT00122382], AMPLE [NCT00929864], AVERT [NCT01142726], AVERT-2 [NCT02504268]) were pooled. Patients were defined as enriched at baseline if they had: 1) RA disease duration ≤ 12 months, 2) DAS28-CRP ≥ 3.2, 3) ≥ 3 times the upper limit of normal on an anti-cyclic citrullinated peptide (anti-CCP) test, and 4) were rheumatoid factor positive (RF+). Patients were grouped according to treatment status (ABA [monotherapy or with methotrexate (MTX)] or non-ABA [MTX or adalimumab (ADA) plus MTX]). Outcomes included DAS28-CRP mean change from baseline to week 24, DAS28-CRP remission and ACR 20/50/70 at week 24. IPD mixed-effects meta-regressions were estimated with trial fixed effects, main effects and interaction of enrichment status and treatment type, trial-level random effects on the interaction, and baseline DAS28-CRP score for DAS28-CRP outcomes. These regressions were conducted in the full population and among ABA patients only. Sensitivity analyses defining enrichment using only criteria 3 and 4 were also conducted.Results:2,087 patients [1,328 (64%) enriched, 759 (36%) non-enriched] were included (AGREE 492 [24%], AMPLE 509 [24%], AVERT 339 [16%], AVERT-2 747 [36%]). Disease duration, RF+, and anti-CCP values differed as expected between the two groups, while DAS28-CRP was high regardless of enrichment status (Table 1). Among ABA-treated patients, outcomes were more favorable for enriched patients compared to non-enriched patients across all outcomes, either statistically or directionally (Figure 1, ABA treatment arm only analysis). The differences in outcomes between enriched vs. non-enriched patients were larger for ABA than for comparators across all outcomes with the exception of ACR 50, where the difference was directionally consistent (Figure 1, ABA vs. comparator analysis). The relative odds of improved efficacy of ABA vs. comparators ranged from 37% to 87% for remission and ACR responses. The results were consistent in the sensitivity analysis using only anti-CCP and RF seropositivity to define enrichment.Figure 1.Analysis resultsConclusion:This post-hoc study corroborates previous evidence of improved outcomes among ABA-treated, seropositive early RA patients by applying eAMPLE inclusion criteria retrospectively to ABA RCTs. The findings support a differential treatment effect for costimulation blockade using ABA among enriched and double antibody positive early RA patients, suggesting a potential for patient-tailored RA treatment approaches.References:[1]Buckner J, et al. Arthritis Rheumatol. 2019; 71 (suppl 10).[2]Huizinga T, et al Annals of the Rheumatic Diseases 2015;74:234-235.[3]Harrold L, et al, Rheumatol Ther. 2019 Jun;6(2):217-230.[4]Sokolove J, et al. Ann Rheum Dis 2016 Apr;75:709–714.Table 1.Baseline characteristicsAll patientsNon-enriched patientsEnriched patientsAbataceptComparatorsAbataceptComparatorsN = 2,087N = 385N = 374N = 784N = 544DemographicsAge (years)49.3 ± 12.949.4 ± 12.650.6 ± 12.948.6 ± 12.549.2 ± 13.5Female79.3%81.3%83.4%77.2%77.9%Disease characteristicsDisease duration (months)8.5 ± 12.519.9 ± 15.918.3 ± 15.12.4 ± 2.82.4 ± 2.9RF Positive91.0%74.2%76.1%100%100%Anti-CCP Positive81.8%52.2%47.3%100%100%DAS28-CRP Score5.71 ± 1.135.72 ± 1.195.66 ± 1.205.68 ± 1.095.76 ± 1.08Comparators included MTX and MTX+ADA.Acknowledgements:This study was sponsored by Bristol Myers Squibb.Disclosure of Interests:Kaleb Michaud Grant/research support from: Pfizer Aspire grant, Sarah (Sang Hee) Park Employee of: Bristol Myers Squibb, Karissa Lozenski Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, John Vaile Shareholder of: Amgen, Novartis, Bristol Myers Squibb, Regeneron, Employee of: Bristol Myers Squibb, Vadim Khaychuk Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Janet Pope Speakers bureau: AbbVie, Amgen, Bristol Myers Squibb, BI, Gilead, Galapagos, Janssen, Lilly, Medexus, Merck, Novartis, Pfizer, Sanofi, Sandoz, Consultant of: AbbVie, Amgen, Bristol Myers Squibb, BI, Celltrion, Gilead, Galapagos, Janssen, Lilly, Medexus, Merck, Novartis, Pfizer, Roche, Samsung, Sanofi, Sandoz, Teva, UCB, Grant/research support from: AbbVie, BMS, Merck, Pfizer, Roche, Seattle Genetics, Philip G Conaghan Speakers bureau: AbbVie, Novartis, Consultant of: Bristol Myers Squibb, Eli Lilly, EMD Serono, Flexion Therapeutics, Galapagos, Gilead, Novartis, Pfizer

Background:During the epidemic’s peak of COVID-19, scientific societies published recommendations on biotherapy and targeted synthetic treatment (B/TST) use in patients with chronic articular inflammatory diseases, inflammatory bowel diseases, and psoriasis.Objectives:The objective was to evaluate the impact of COVID-19 in France on initiation and renewal of B/TST.Methods:LRx contains all anonymized medication dispenses prescribed in outpatient care in a representative panel of French retails pharmacies, including data of near 40 million patients. The impact of B/TST initiation and renewal were studied using 2019 as reference and dispense deliveries data of pharmacies with regular flew in order to perform the comparison. B/TST considered were abatacept, anti-TNF, anti-IL6, anti-IL17, anti-IL12/23 or anti-IL23, JAK inhibitors (JAKi) and other classes such as aprelimast, aminosalicylates (AS), hydroxychloroquine (HCQ), and methotrexate (MTX). A treatment initiated was defined as a treatment not delivered in the past 12 months, and conversely for a treatment renewal. Results were presented as raw one and expressed in percentage of patients having at least one B/TST delivery in each therapeutic classes of interest in 2020 compared to 2019 used as reference year (period from week 12 to week 19 considered and corresponding to the lockdown period in France).Results:During the lockdown period, a decrease in initiation was observed for patients treated with: abatacept (405 in 2019 vs 227 in 2020: -44%, pConclusion:During the epidemic’s peak, initiation of AS, MTX, biotherapies (except for tocilizumab), and JAKi dramatically decreased without impacting their renewal. Two treatments were mainly initiated, tocilizumab probably due to a switch from intravenous to subcutaneous injection and HCQ in relation to its presumably effect on COVID-19. Overall, recommendations from scientific societies have been followed.Disclosure of Interests:None declared

Background:Abatacept (ABA) is a selective T-cell co-stimulatory modulator. After its approval, changes in therapeutic recommendations, the arrival of new drugs (e.g., biosimilars or Janus kinase inhibitors) and growing focus on comprehensive patient care may have changed prescription patterns, channeling ABA use towards specific patient subtypes. To date, studies analyzing these aspects in clinical practice settings are scarce.Objectives:We aimed to evaluate the epidemiological profile of ABA users and compare it to other DMARD groups included in the register.Methods:We performed an observational study based on the nationwide Spanish register BIOBADASER, which includes patients with rheumatic diseases receiving biologic disease-modifying antirheumatic drugs (bDMARDs) or targeted synthetic DMARDs (tsDMARDs) from 28 tertiary centers. For this analysis, all RA patients included from December 2015 to December 2020 were examined. Baseline features were analyzed descriptively grouping all b/tsDMARDs by mode of action. Clinical effectiveness was assessed through drug survival obtained by the Kaplan-Meier method. Patients were right-censored if data were not available if they were still on treatment at the time of data analysis. The safety profile was assessed by the adverse events (AE) and serious AE incidence rates (IR) expressed as events per 1000 patient-years.Results:There were 628 ABA-treated patients, 471 (75%) using the subcutaneous presentation. Only 142 (23%) were on first-line while 381 (61%) were on third or later-line therapy. ABA users were older and more likely to present certain comorbidities compared to the other b/tsDMARD groups. The biggest relative differences were seen for interstitial lung disease (ILD), chronic obstructive pulmonary disease (COPD), diabetes and ischemic heart disease. (Table 1)Table 1.This 12-month interim analysis includes 496 patients (336 with axSpA, 98 with RA and 62 with PsA)NABAIL-6CD20JAKiTNFi6287861816691787Mean age, years (SD)64.1 (12.0)50.7 (12.7)63.2 (12.3)59.6 (12.3)60.7 (13.1)Female sex, n (%)482 (77)652 (83)135 (75)537 (80)1418 (79)Median disease duration (p25-p75)10.1 (5.1-16.5)9.4 (4.6-15.9)13.3 (8.3-20.6)10.4 (5.0-17.2)7.4 (3.2-13.7)ACPA, n (%)352 (72)425 (71)113 (79)407 (70)875 (70)RF, n (%)380 (77)454 (75)124 (86)411 (70)915 (72)Current smokers, n (%)98 (16)137 (17)338 (19)90 (20)259 (18)ILD, n (%)64 (13)21 (3)25 (2)8 (2)19 (2)COPD, n (%)38 (6)23(3)52 (3)14 (3)43 (3)Chronic Kidney Disease, n (%)18 (3)13 (2)19 (1)13 (3)18 (1)Diabetes73 (12)66 (8)13 (7)46 (10)100 (7)Ischemic Heart Disease, n (%)36 (6)23 (3)012 (3)30 (2)Hypertension, n (%)197 (31)198 (25)416 (23)131 (30)338 (23)Heart Failure, n (%)19 (4)12 (2)10 (1)6 (2)5 (1)Osteoporosis, n (%)133 (21)141 (18)26 (14)72 (16)215 (15)IL-6: Tocilizumab and Sarilumab; CD20: Rituximab and biosimilars; JAKi: Janus kinase inhibitors (Tofacitinib and Baricitinib); TNFi: TNF inhibitors and biosimilars; ACPA: anti-citrullinated peptide antibodies; RF: rheumatoid factor; ILD: interstitial lung disease; COPD: chronic obstructive pulmonary disease.Overall, 63% of patients remained on ABA at 1 year, 48% at 2 and 31% at 5 years after drug initiation. The corresponding proportions were 79%, 65% and 52% for bionaïve and 59%, 43% and 30% for those in third or later-line therapy. From 394 total discontinuations, loss of efficacy in 225 (57%) and AE in 98 (25%) were the main reasons. This trend was consistent among all therapy lines.The total IR of AE was 886.5 (837.3-938.5) and 156.4 (136.5-179.2) for SAE. Infections were the most frequent AE overall, IR 44.4 (34.4-57.3), and the highest IR was seen among bionaïve patients (69.6 (44.9-107.9)).Conclusion:ABA-treated RA patients in Spain are older and have more comorbidities (vs other b/tsDMARDs), especially ILD, COPD, ischemic heart disease and diabetes and receive ABA as third or later-line therapy. Although these features are associated with worse response to treatment and a higher risk of infection, ABA presents a good drug survival and infectious AE are not the main cause of discontinuation.Acknowledgements:On behalf of the BIOBADASER Working groupDisclosure of Interests:Sebastián C Rodriguez-García Speakers bureau: Sanofi, MSD, UCB-Pharma, Bristol-Myers-Squibb, Novartis, Janssen, Consultant of: Bristol-Myers-Squibb, Galápagos, Carlos Sánchez-Piedra: None declared, Raul Castellanos-Moreira Speakers bureau: Roche, Sanofi, MSD, UCB-Pharma, Bristol-Myers-Squibb, Novartis, Lilly, and Pfizer., Dolores Ruiz-Montesinos: None declared, Manuel Pombo: None declared, Fernando Sánchez-Alonso: None declared, Juan J. Gómez-Reino Consultant of: Pfizer, Grant/research support from: Abbvie, Lilly, MSD, Pfizer, Roche, and UCB.

Background:The semi-quantitative Outcome Measures in Rheumatology (OMERACT) Psoriatic Arthritis Magnetic Resonance Imaging Score (PsAMRIS) was developed for the evaluation of inflammatory and destructive changes in PsA,1 but has limited trial usage.Objectives:To retrospectively utilise the PsAMRIS in a multi-dose, randomised Phase IIb study of abatacept in patients with PsA who have inadequate response to DMARDs (NCT00534313).2Methods:Patients were randomised to abatacept (3, 10 or 30/10 mg/kg [the 30-mg/kg group switched to 10 mg/kg after the first two doses]) or placebo and treated for 169 days, after which all patients received abatacept 10 mg/kg through to Day 365. MRI scans of one hand or foot from 123 patients with PsA collected at baseline and on Days 85, 169 and 365 were centrally evaluated by two readers blinded to chronological order and treatment arm. Synovitis, bone oedema, tenosynovitis, periarticular inflammation, bone erosion, bone proliferation and joint space narrowing were assessed as per OMERACT PsAMRIS; a novel total inflammation score was calculated from the sum of synovitis, bone oedema, tenosynovitis and periarticular inflammation. Variables were analysed using all cases (hand or foot) and by hand and foot cases separately.Results:At Day 169, the abatacept 30/10 mg/kg or 10 mg/kg group showed the most decrease (improvement) in each inflammatory assessment (Figure 1). The Day 169 change from baseline severity in synovitis and tenosynovitis in the abatacept 30/10 mg/kg and 10 mg/kg groups, respectively, were significantly reduced (improved) compared with placebo (estimated differences of –0.966 [p=0.039] and –1.652 [p=0.014], respectively) (Table 1). Patients originally randomised to placebo and then switched to abatacept 10 mg/kg at Day 169 showed significant improvements in synovitis, tenosynovitis and total inflammation from Day 169 to Day 365 (Table 1, Figure 1). The structural outcomes joint space narrowing and bone erosion remained stable within each treatment group, showing little change from baseline to Days 85, 169 and 365. After separating hand and foot analyses (72 hand and 51 foot cases), only hand tenosynovitis in the 10-mg/kg group and foot synovitis in the 3-mg/kg group were significantly reduced (improved) at Day 169 compared with placebo (differences of –2.331 [p=0.017] and –1.689 [p=0.010], respectively). In general, more comparisons in the hand analysis were statistically significant versus in the foot analysis.Conclusion:This analysis confirmed the efficacy of abatacept 10 and 30/10 mg/kg when assessed with the OMERACT PsAMRIS. The inflammatory pathologies, synovitis and tenosynovitis, appeared to be the most responsive MRI outcomes. Analysing hand and foot cases together yielded results consistent with the primary clinical efficacy endpoint (ACR20 response rate), as the abatacept 10- and 30/10-mg/kg groups showed significant differences versus placebo at Day 169;2 reduced sample size in separate hand and foot assessments may have prevented finding significant results corresponding to the combined analysis. These results also demonstrate the responsiveness of the PsAMRIS in PsA randomised clinical trials.References:[1]Glinatsi D, et al. J Rheumatol 2015;42:2473–2479.[2]Mease P, et al. Arthritis Rheum 2011;63:939–948.Table 1.MRI variables showing significant treatment effectsaBetween groups at Day 169MRI scoreComparatorComparatorDifferenceSEp valueSynovitisPlaceboAbatacept 30/10 mg/kg–0.9660.4610.039TenosynovitisPlaceboAbatacept 10 mg/kg–1.6520.6620.014Placebo group before/after switchbMRI scoreTreatment, Day 169Treatment, Day 365DifferenceSEp valueSynovitisPlaceboAbatacept 10 mg/kg–1.0180.4580.029TenosynovitisPlaceboAbatacept 10 mg/kg–0.9400.3900.018Total inflammationPlaceboAbatacept 10 mg/kg–2.2751.0670.036aBased on change from baseline at the stated time points (unadjusted p values).bPatients were switched to abatacept 10 mg/kg after Day 169.Acknowledgements:Professional medical writing and editorial assistance was provided by Rob Coover, MPH, at Caudex and was funded by Bristol Myers Squibb.Disclosure of Interests:Mikkel Østergaard Speakers bureau: AbbVie, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, Roche, Sanofi, UCB, Consultant of: AbbVie, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Hospira, Janssen, Merck, Novartis, Novo, Orion, Pfizer, Regeneron, Roche, Sandoz, Sanofi, UCB, Grant/research support from: AbbVie, Bristol Myers Squibb, Celgene, Merck, Novartis, Paul Bird Speakers bureau: AbbVie, Bristol Myers Squibb, Eli Lilly, Novartis, Pfizer, UCB, Grant/research support from: Gilead, Chahin Pachai Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Shuyan Du Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Chun Wu Employee of: Bristol Myers Squibb, Jessica Landis Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Thomas Fuerst Employee of: Bioclinica, Inc., a contract research service providing radiology central reading services to pharmaceutical, biotech and medical device companies, Harris A Ahmad Employee of: Bristol Myers Squibb, Sean Connolly Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Philip G Conaghan Speakers bureau: AbbVie, Novartis, Consultant of: AstraZeneca, Bristol Myers Squibb, Eli Lilly, EMD Serono, Flexion Therapeutics, Galapagos, Gilead, Novartis, Pfizer.

Background:Among therapeutics used to treat rheumatoid arthritis (RA), Tocilizumab (TCZ) and Abatacept (ABA) are both biologic agents that can be delivered subcutaneously (SC) or intravenously (IV). During the first COVID-19 lockdown in France, all patients treated with IV TCZ or IV ABA were offered the option to switch to SC administration.Objectives:The primary aim was to assess the impact of changing the route of administration on the disease activity. The second aim was to assess whether the return to IV route at the patient’s request was associated with disease activity variation, flares, anxiety, depression and low physical activity during the lockdown.Methods:We conducted a prospective monocentric observational study. Eligibility criteria: Adult ≥ 18 years old, RA treated with IV TCZ or IV ABA with a stable dose ≥3 months, change in administration route (from IV to SC) between March 16, 2020, and April 17, 2020. The following data were collected at baseline and 6 months later (M6): demographics, RA characteristics, treatment, history of previous SC treatment, disease activity (DAS28), self-administered questionnaires on flares, RA life repercussions, physical activity, anxiety and depression (FLARE, RAID, Ricci &Gagnon, HAD).The primary outcome was the proportion of patients with a DAS28 variation>1.2 at M6. Analyses: Chi2-test for quantitative variables and Mann-Whitney test for qualitative variables. Factors associated with return to IV route identification was performed with univariate and multivariate analysis.Results:Among the 84 patients who were offered to switch their treatment route of administration, 13 refused to change their treatment. Among the 71 who switched (48 TCZ, 23 ABA), 58 had a M6 follow-up visit (13 lost of follow-up) and DAS28 was available for 49 patients at M6. Main baseline characteristics: female 81%, mean age 62.7, mean disease duration: 16.0, ACPA positive: 72.4%, mean DAS28: 2.01, previously treated with SC TCZ or ABA: 17%.At M6, the mean DAS28 variation was 0.18 ± 0.15. Ten (12.2%) patients had a DAS28 worsening>1.2 (ABA: 5/17 [29.4%] and TCZ: 5/32 [15.6%], p= 0.152) and 19 patients (32.8%) had a DAS28 worsening>0.6 (ABA: 11/17 [64.7%] and TCZ: 8/32 [25.0%], p= 0.007).At M6, 41 patients (77.4%) were back to IV route (26 TCZ, 15 ABA) at their request. The proportion of patients with a DAS28 worsening>1.2 and>0.6 in the groups return to IV versus SC maintenance were 22.5%, 42.5% versus 11.1% and 22.2% (p=0.4), respectively. The univariate analysis identified the following factors associated with the return to IV route: HAD depression score (12 vs 41, p=0.009), HAS anxiety score (12 vs 41, p=0.047) and corticosteroid use (70% vs 100%, p=0.021), in the SC maintenance vs return to IV, respectively.Conclusion:The change of administration route of TCZ and ABA during the first COVID-19 lockdown was infrequently associated with a worsening of RA disease. However, the great majority of the patients (77.4%) request to return to IV route, even without disease activity worsening. This nocebo effect was associated with higher anxiety and depression scores.Disclosure of Interests:None declared